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Inga-lill Mårtensson - One of the best experts on this subject based on the ideXlab platform.
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transcription of productive and nonproductive vdj recombined alleles after igh Allelic Exclusion
The EMBO Journal, 2007Co-Authors: Janssen Daly, Steve Licence, Aikaterini Nanou, Geoff Morgan, Inga-lill MårtenssonAbstract:The process of Allelic Exclusion ensures that each B cell expresses a B-cell receptor encoded by only one of its Ig heavy (IgH) and light (IgL) chain alleles. Although its precise mechanism is unknown, recruitment of the nonfunctional IgH allele to centromeric heterochromatin correlates with the establishment of Allelic Exclusion. Similarly, recruitment in activated splenic B cells correlates with cell division. In the latter, the recruited IgH allele was reported to be transcriptionally silent. However, it is not known whether monoAllelic recruitment during establishment of Allelic Exclusion correlates with transcriptional silencing. To investigate this, we assessed the transcriptional status of both IgH alleles in single primary cells over the course of B-cell development, using RNA fluorescence in situ hybridization. Before Allelic Exclusion both alleles are transcribed. Thereafter, in pre-BII and subsequent developmental stages both functional and nonfunctional VDJ- and DJ-transcription is observed. Thus, after the establishment of IgH Allelic Exclusion, monoAllelic recruitment to heterochromatin does not silence VDJ- or DJ-transcription, but serves another purpose.
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Transcription of productive and nonproductive VDJ‐recombined alleles after IgH Allelic Exclusion
The EMBO journal, 2007Co-Authors: Janssen Daly, Steve Licence, Aikaterini Nanou, Geoff Morgan, Inga-lill MårtenssonAbstract:The process of Allelic Exclusion ensures that each B cell expresses a B-cell receptor encoded by only one of its Ig heavy (IgH) and light (IgL) chain alleles. Although its precise mechanism is unknown, recruitment of the nonfunctional IgH allele to centromeric heterochromatin correlates with the establishment of Allelic Exclusion. Similarly, recruitment in activated splenic B cells correlates with cell division. In the latter, the recruited IgH allele was reported to be transcriptionally silent. However, it is not known whether monoAllelic recruitment during establishment of Allelic Exclusion correlates with transcriptional silencing. To investigate this, we assessed the transcriptional status of both IgH alleles in single primary cells over the course of B-cell development, using RNA fluorescence in situ hybridization. Before Allelic Exclusion both alleles are transcribed. Thereafter, in pre-BII and subsequent developmental stages both functional and nonfunctional VDJ- and DJ-transcription is observed. Thus, after the establishment of IgH Allelic Exclusion, monoAllelic recruitment to heterochromatin does not silence VDJ- or DJ-transcription, but serves another purpose.
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VpreB1/VpreB2/λ5 Triple-Deficient Mice Show Impaired B Cell Development but Functional Allelic Exclusion of the IgH Locus
Journal of immunology (Baltimore Md. : 1950), 2002Co-Authors: Takeyuki Shimizu, Steve Licence, Cornelia Mundt, Fritz Melchers, Inga-lill MårtenssonAbstract:At the precursor B cell stage during bone marrow B cell development, Ig μH chain associates with surrogate L (SL) chain, which is encoded by the three genes VpreB1 , VpreB2 , and λ 5 , to form the pre-B cell receptor (pre-BCR). Surface expression of the pre-BCR is believed to signal both proliferation and Allelic Exclusion of the IgH locus. Mice which lack either VpreB1 / VpreB2 or λ 5 show a lack of precursor B cell expansion but normal IgH Allelic Exclusion. This would suggest that one of either λ5 or VpreB can make a pre-BCR-like complex which is still able to signal Allelic Exclusion but not proliferation. To investigate this, we established mice lacking all components of the SL chain. These mice showed severely impaired B cell development which was similar to that previously found in mice lacking either λ 5 or VpreB1 / VpreB2 . Surprisingly, the IgH locus was still Allelically excluded and thus the SL chain appears not to be involved in Allelic Exclusion.
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vpreb1 vpreb2 λ5 triple deficient mice show impaired b cell development but functional Allelic Exclusion of the igh locus
Journal of Immunology, 2002Co-Authors: Takeyuki Shimizu, Steve Licence, Cornelia Mundt, Fritz Melchers, Inga-lill MårtenssonAbstract:At the precursor B cell stage during bone marrow B cell development, Ig μH chain associates with surrogate L (SL) chain, which is encoded by the three genes VpreB1 , VpreB2 , and λ 5 , to form the pre-B cell receptor (pre-BCR). Surface expression of the pre-BCR is believed to signal both proliferation and Allelic Exclusion of the IgH locus. Mice which lack either VpreB1 / VpreB2 or λ 5 show a lack of precursor B cell expansion but normal IgH Allelic Exclusion. This would suggest that one of either λ5 or VpreB can make a pre-BCR-like complex which is still able to signal Allelic Exclusion but not proliferation. To investigate this, we established mice lacking all components of the SL chain. These mice showed severely impaired B cell development which was similar to that previously found in mice lacking either λ 5 or VpreB1 / VpreB2 . Surprisingly, the IgH locus was still Allelically excluded and thus the SL chain appears not to be involved in Allelic Exclusion.
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The pre-B cell receptor and its role in proliferation and Ig heavy chain Allelic Exclusion
Seminars in immunology, 2002Co-Authors: Inga-lill Mårtensson, Steve Licence, Cornelia Mundt, Fritz Melchers, Antonius G. Rolink, Takeyuki ShimizuAbstract:Abstract The pre-B cell receptor (pre-BCR) is composed of the immunoglobulin (Ig) heavy ( μ H) chain and the surrogate light chain encoded by VpreB and λ 5. The pre-BCR has been implicated in precursor B cell proliferation, differentiation and IgH chain Allelic Exclusion. B cell development in mice lacking the transmembrane form of μ H chain is blocked at the precursor B cell stage: the cells cannot proliferate or differentiate further and the IgH locus is Allelically included. In mice lacking λ 5, the precursor B cells, although unable to proliferate, can nonetheless differentiate, whereas the IgH locus is Allelically excluded. It was, therefore, postulated that μ H chain together with VpreB could form a pre-BCR-like receptor that would allow IgH Allelic Exclusion but not proliferation. In mice lacking both VpreB genes, precursor B cells do not proliferate but are able to differentiate. Surprisingly, the IgH locus is Allelically excluded. This suggests that μ H chains find other partner proteins to signal Allelic Exclusion.
Takeyuki Shimizu - One of the best experts on this subject based on the ideXlab platform.
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VpreB1/VpreB2/λ5 Triple-Deficient Mice Show Impaired B Cell Development but Functional Allelic Exclusion of the IgH Locus
Journal of immunology (Baltimore Md. : 1950), 2002Co-Authors: Takeyuki Shimizu, Steve Licence, Cornelia Mundt, Fritz Melchers, Inga-lill MårtenssonAbstract:At the precursor B cell stage during bone marrow B cell development, Ig μH chain associates with surrogate L (SL) chain, which is encoded by the three genes VpreB1 , VpreB2 , and λ 5 , to form the pre-B cell receptor (pre-BCR). Surface expression of the pre-BCR is believed to signal both proliferation and Allelic Exclusion of the IgH locus. Mice which lack either VpreB1 / VpreB2 or λ 5 show a lack of precursor B cell expansion but normal IgH Allelic Exclusion. This would suggest that one of either λ5 or VpreB can make a pre-BCR-like complex which is still able to signal Allelic Exclusion but not proliferation. To investigate this, we established mice lacking all components of the SL chain. These mice showed severely impaired B cell development which was similar to that previously found in mice lacking either λ 5 or VpreB1 / VpreB2 . Surprisingly, the IgH locus was still Allelically excluded and thus the SL chain appears not to be involved in Allelic Exclusion.
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vpreb1 vpreb2 λ5 triple deficient mice show impaired b cell development but functional Allelic Exclusion of the igh locus
Journal of Immunology, 2002Co-Authors: Takeyuki Shimizu, Steve Licence, Cornelia Mundt, Fritz Melchers, Inga-lill MårtenssonAbstract:At the precursor B cell stage during bone marrow B cell development, Ig μH chain associates with surrogate L (SL) chain, which is encoded by the three genes VpreB1 , VpreB2 , and λ 5 , to form the pre-B cell receptor (pre-BCR). Surface expression of the pre-BCR is believed to signal both proliferation and Allelic Exclusion of the IgH locus. Mice which lack either VpreB1 / VpreB2 or λ 5 show a lack of precursor B cell expansion but normal IgH Allelic Exclusion. This would suggest that one of either λ5 or VpreB can make a pre-BCR-like complex which is still able to signal Allelic Exclusion but not proliferation. To investigate this, we established mice lacking all components of the SL chain. These mice showed severely impaired B cell development which was similar to that previously found in mice lacking either λ 5 or VpreB1 / VpreB2 . Surprisingly, the IgH locus was still Allelically excluded and thus the SL chain appears not to be involved in Allelic Exclusion.
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The pre-B cell receptor and its role in proliferation and Ig heavy chain Allelic Exclusion
Seminars in immunology, 2002Co-Authors: Inga-lill Mårtensson, Steve Licence, Cornelia Mundt, Fritz Melchers, Antonius G. Rolink, Takeyuki ShimizuAbstract:Abstract The pre-B cell receptor (pre-BCR) is composed of the immunoglobulin (Ig) heavy ( μ H) chain and the surrogate light chain encoded by VpreB and λ 5. The pre-BCR has been implicated in precursor B cell proliferation, differentiation and IgH chain Allelic Exclusion. B cell development in mice lacking the transmembrane form of μ H chain is blocked at the precursor B cell stage: the cells cannot proliferate or differentiate further and the IgH locus is Allelically included. In mice lacking λ 5, the precursor B cells, although unable to proliferate, can nonetheless differentiate, whereas the IgH locus is Allelically excluded. It was, therefore, postulated that μ H chain together with VpreB could form a pre-BCR-like receptor that would allow IgH Allelic Exclusion but not proliferation. In mice lacking both VpreB genes, precursor B cells do not proliferate but are able to differentiate. Surprisingly, the IgH locus is Allelically excluded. This suggests that μ H chains find other partner proteins to signal Allelic Exclusion.
Steve Licence - One of the best experts on this subject based on the ideXlab platform.
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transcription of productive and nonproductive vdj recombined alleles after igh Allelic Exclusion
The EMBO Journal, 2007Co-Authors: Janssen Daly, Steve Licence, Aikaterini Nanou, Geoff Morgan, Inga-lill MårtenssonAbstract:The process of Allelic Exclusion ensures that each B cell expresses a B-cell receptor encoded by only one of its Ig heavy (IgH) and light (IgL) chain alleles. Although its precise mechanism is unknown, recruitment of the nonfunctional IgH allele to centromeric heterochromatin correlates with the establishment of Allelic Exclusion. Similarly, recruitment in activated splenic B cells correlates with cell division. In the latter, the recruited IgH allele was reported to be transcriptionally silent. However, it is not known whether monoAllelic recruitment during establishment of Allelic Exclusion correlates with transcriptional silencing. To investigate this, we assessed the transcriptional status of both IgH alleles in single primary cells over the course of B-cell development, using RNA fluorescence in situ hybridization. Before Allelic Exclusion both alleles are transcribed. Thereafter, in pre-BII and subsequent developmental stages both functional and nonfunctional VDJ- and DJ-transcription is observed. Thus, after the establishment of IgH Allelic Exclusion, monoAllelic recruitment to heterochromatin does not silence VDJ- or DJ-transcription, but serves another purpose.
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Transcription of productive and nonproductive VDJ‐recombined alleles after IgH Allelic Exclusion
The EMBO journal, 2007Co-Authors: Janssen Daly, Steve Licence, Aikaterini Nanou, Geoff Morgan, Inga-lill MårtenssonAbstract:The process of Allelic Exclusion ensures that each B cell expresses a B-cell receptor encoded by only one of its Ig heavy (IgH) and light (IgL) chain alleles. Although its precise mechanism is unknown, recruitment of the nonfunctional IgH allele to centromeric heterochromatin correlates with the establishment of Allelic Exclusion. Similarly, recruitment in activated splenic B cells correlates with cell division. In the latter, the recruited IgH allele was reported to be transcriptionally silent. However, it is not known whether monoAllelic recruitment during establishment of Allelic Exclusion correlates with transcriptional silencing. To investigate this, we assessed the transcriptional status of both IgH alleles in single primary cells over the course of B-cell development, using RNA fluorescence in situ hybridization. Before Allelic Exclusion both alleles are transcribed. Thereafter, in pre-BII and subsequent developmental stages both functional and nonfunctional VDJ- and DJ-transcription is observed. Thus, after the establishment of IgH Allelic Exclusion, monoAllelic recruitment to heterochromatin does not silence VDJ- or DJ-transcription, but serves another purpose.
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VpreB1/VpreB2/λ5 Triple-Deficient Mice Show Impaired B Cell Development but Functional Allelic Exclusion of the IgH Locus
Journal of immunology (Baltimore Md. : 1950), 2002Co-Authors: Takeyuki Shimizu, Steve Licence, Cornelia Mundt, Fritz Melchers, Inga-lill MårtenssonAbstract:At the precursor B cell stage during bone marrow B cell development, Ig μH chain associates with surrogate L (SL) chain, which is encoded by the three genes VpreB1 , VpreB2 , and λ 5 , to form the pre-B cell receptor (pre-BCR). Surface expression of the pre-BCR is believed to signal both proliferation and Allelic Exclusion of the IgH locus. Mice which lack either VpreB1 / VpreB2 or λ 5 show a lack of precursor B cell expansion but normal IgH Allelic Exclusion. This would suggest that one of either λ5 or VpreB can make a pre-BCR-like complex which is still able to signal Allelic Exclusion but not proliferation. To investigate this, we established mice lacking all components of the SL chain. These mice showed severely impaired B cell development which was similar to that previously found in mice lacking either λ 5 or VpreB1 / VpreB2 . Surprisingly, the IgH locus was still Allelically excluded and thus the SL chain appears not to be involved in Allelic Exclusion.
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vpreb1 vpreb2 λ5 triple deficient mice show impaired b cell development but functional Allelic Exclusion of the igh locus
Journal of Immunology, 2002Co-Authors: Takeyuki Shimizu, Steve Licence, Cornelia Mundt, Fritz Melchers, Inga-lill MårtenssonAbstract:At the precursor B cell stage during bone marrow B cell development, Ig μH chain associates with surrogate L (SL) chain, which is encoded by the three genes VpreB1 , VpreB2 , and λ 5 , to form the pre-B cell receptor (pre-BCR). Surface expression of the pre-BCR is believed to signal both proliferation and Allelic Exclusion of the IgH locus. Mice which lack either VpreB1 / VpreB2 or λ 5 show a lack of precursor B cell expansion but normal IgH Allelic Exclusion. This would suggest that one of either λ5 or VpreB can make a pre-BCR-like complex which is still able to signal Allelic Exclusion but not proliferation. To investigate this, we established mice lacking all components of the SL chain. These mice showed severely impaired B cell development which was similar to that previously found in mice lacking either λ 5 or VpreB1 / VpreB2 . Surprisingly, the IgH locus was still Allelically excluded and thus the SL chain appears not to be involved in Allelic Exclusion.
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The pre-B cell receptor and its role in proliferation and Ig heavy chain Allelic Exclusion
Seminars in immunology, 2002Co-Authors: Inga-lill Mårtensson, Steve Licence, Cornelia Mundt, Fritz Melchers, Antonius G. Rolink, Takeyuki ShimizuAbstract:Abstract The pre-B cell receptor (pre-BCR) is composed of the immunoglobulin (Ig) heavy ( μ H) chain and the surrogate light chain encoded by VpreB and λ 5. The pre-BCR has been implicated in precursor B cell proliferation, differentiation and IgH chain Allelic Exclusion. B cell development in mice lacking the transmembrane form of μ H chain is blocked at the precursor B cell stage: the cells cannot proliferate or differentiate further and the IgH locus is Allelically included. In mice lacking λ 5, the precursor B cells, although unable to proliferate, can nonetheless differentiate, whereas the IgH locus is Allelically excluded. It was, therefore, postulated that μ H chain together with VpreB could form a pre-BCR-like receptor that would allow IgH Allelic Exclusion but not proliferation. In mice lacking both VpreB genes, precursor B cells do not proliferate but are able to differentiate. Surprisingly, the IgH locus is Allelically excluded. This suggests that μ H chains find other partner proteins to signal Allelic Exclusion.
Bryce A. Binstadt - One of the best experts on this subject based on the ideXlab platform.
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incomplete tcr β Allelic Exclusion accelerates spontaneous autoimmune arthritis in k bxn tcr transgenic mice
European Journal of Immunology, 2012Co-Authors: Jennifer L. Auger, Stefanie Haasken, Elizabeth M. Steinert, Bryce A. BinstadtAbstract:Allelic Exclusion of antigen receptor loci is a fundamental mechanism of immunological self-tolerance. Incomplete Allelic Exclusion leads to dual T-cell receptor (TCR) expression and can allow developing autoreactive αβ T lymphocytes to escape clonal deletion. Because Allelic Exclusion at the TCR-β locus is more stringent than at the TCR-α locus, dual TCR-β expression has not been considered a likely contributor to autoimmunity. We show here that incomplete TCR-β Allelic Exclusion permits developing thymocytes bearing the autoreactive, transgene-encoded KRN TCR to be positively selected more efficiently, thereby accelerating the onset of spontaneous autoimmune arthritis. Our findings highlight dual TCR-β expression as a mechanism that can enhance the maturation of autoreactive pathogenic T cells and lead to more rapid development of autoimmune disease.
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Incomplete TCR‐β Allelic Exclusion accelerates spontaneous autoimmune arthritis in K/BxN TCR transgenic mice
European journal of immunology, 2012Co-Authors: Jennifer L. Auger, Stefanie Haasken, Elizabeth M. Steinert, Bryce A. BinstadtAbstract:Allelic Exclusion of antigen receptor loci is a fundamental mechanism of immunological self-tolerance. Incomplete Allelic Exclusion leads to dual T-cell receptor (TCR) expression and can allow developing autoreactive αβ T lymphocytes to escape clonal deletion. Because Allelic Exclusion at the TCR-β locus is more stringent than at the TCR-α locus, dual TCR-β expression has not been considered a likely contributor to autoimmunity. We show here that incomplete TCR-β Allelic Exclusion permits developing thymocytes bearing the autoreactive, transgene-encoded KRN TCR to be positively selected more efficiently, thereby accelerating the onset of spontaneous autoimmune arthritis. Our findings highlight dual TCR-β expression as a mechanism that can enhance the maturation of autoreactive pathogenic T cells and lead to more rapid development of autoimmune disease.
Fritz Melchers - One of the best experts on this subject based on the ideXlab platform.
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VpreB1/VpreB2/λ5 Triple-Deficient Mice Show Impaired B Cell Development but Functional Allelic Exclusion of the IgH Locus
Journal of immunology (Baltimore Md. : 1950), 2002Co-Authors: Takeyuki Shimizu, Steve Licence, Cornelia Mundt, Fritz Melchers, Inga-lill MårtenssonAbstract:At the precursor B cell stage during bone marrow B cell development, Ig μH chain associates with surrogate L (SL) chain, which is encoded by the three genes VpreB1 , VpreB2 , and λ 5 , to form the pre-B cell receptor (pre-BCR). Surface expression of the pre-BCR is believed to signal both proliferation and Allelic Exclusion of the IgH locus. Mice which lack either VpreB1 / VpreB2 or λ 5 show a lack of precursor B cell expansion but normal IgH Allelic Exclusion. This would suggest that one of either λ5 or VpreB can make a pre-BCR-like complex which is still able to signal Allelic Exclusion but not proliferation. To investigate this, we established mice lacking all components of the SL chain. These mice showed severely impaired B cell development which was similar to that previously found in mice lacking either λ 5 or VpreB1 / VpreB2 . Surprisingly, the IgH locus was still Allelically excluded and thus the SL chain appears not to be involved in Allelic Exclusion.
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vpreb1 vpreb2 λ5 triple deficient mice show impaired b cell development but functional Allelic Exclusion of the igh locus
Journal of Immunology, 2002Co-Authors: Takeyuki Shimizu, Steve Licence, Cornelia Mundt, Fritz Melchers, Inga-lill MårtenssonAbstract:At the precursor B cell stage during bone marrow B cell development, Ig μH chain associates with surrogate L (SL) chain, which is encoded by the three genes VpreB1 , VpreB2 , and λ 5 , to form the pre-B cell receptor (pre-BCR). Surface expression of the pre-BCR is believed to signal both proliferation and Allelic Exclusion of the IgH locus. Mice which lack either VpreB1 / VpreB2 or λ 5 show a lack of precursor B cell expansion but normal IgH Allelic Exclusion. This would suggest that one of either λ5 or VpreB can make a pre-BCR-like complex which is still able to signal Allelic Exclusion but not proliferation. To investigate this, we established mice lacking all components of the SL chain. These mice showed severely impaired B cell development which was similar to that previously found in mice lacking either λ 5 or VpreB1 / VpreB2 . Surprisingly, the IgH locus was still Allelically excluded and thus the SL chain appears not to be involved in Allelic Exclusion.
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The pre-B cell receptor and its role in proliferation and Ig heavy chain Allelic Exclusion
Seminars in immunology, 2002Co-Authors: Inga-lill Mårtensson, Steve Licence, Cornelia Mundt, Fritz Melchers, Antonius G. Rolink, Takeyuki ShimizuAbstract:Abstract The pre-B cell receptor (pre-BCR) is composed of the immunoglobulin (Ig) heavy ( μ H) chain and the surrogate light chain encoded by VpreB and λ 5. The pre-BCR has been implicated in precursor B cell proliferation, differentiation and IgH chain Allelic Exclusion. B cell development in mice lacking the transmembrane form of μ H chain is blocked at the precursor B cell stage: the cells cannot proliferate or differentiate further and the IgH locus is Allelically included. In mice lacking λ 5, the precursor B cells, although unable to proliferate, can nonetheless differentiate, whereas the IgH locus is Allelically excluded. It was, therefore, postulated that μ H chain together with VpreB could form a pre-BCR-like receptor that would allow IgH Allelic Exclusion but not proliferation. In mice lacking both VpreB genes, precursor B cells do not proliferate but are able to differentiate. Surprisingly, the IgH locus is Allelically excluded. This suggests that μ H chains find other partner proteins to signal Allelic Exclusion.
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Precursor B Cells Showing H Chain Allelic Inclusion Display Allelic Exclusion at the Level of Pre-B Cell Receptor Surface Expression
Immunity, 1998Co-Authors: Edwin Ten Boekel, Fritz Melchers, Antonius G. RolinkAbstract:Within the pools of muH chain-producing precursor and mature B cells from normal and lambda5-defective mice, the frequency of cells in which both H chain alleles were productively VHDJH rearranged was determined. An equally high percentage (2%-4%) of cells carrying two productively VHDJH-rearranged H chain loci was found in precursor and mature B cell pools of both mouse strains. In all of these cells, one allele encodes a muH chain incapable of forming a surface-expressed pre-B cell receptor. Hence, Allelic Exclusion is maintained at the level of pre-B cell receptor expression. The surprising conservation of H chain Allelic Exclusion in lambda5-defective B cells suggests that an alternative form of pre-B cell receptor might function to ensure this Allelic Exclusion.