Selective maturation of VH12 B cells in the spleen enriches for anti-phosphatidyl choline B cells: evidence for receptor editing.
PtC-specific B-1 cells originate from conventional B-2 (B-0) cells as a result of antigen activation. VH12 B cells specific for PtC are enriched at two developmental checkpoints in the bone marrow; first at the pre-BI to pre-BII transition where VH12 pre-B cells with anti-PtC VHCDR3 are enriched, and second at the pre-BII to immature B cell transition where L chain diversity is restricted. This restriction is due to the inability of most L chains to associate with VH12 H chains. We present evidence here of a third developmental checkpoint that enriches for PtC-specific B cells, at the transitional to mature B-2 (B-0) cell stage. Most VH12 transitional B cells do not differentiate to a mature B-2 cell and, of those that do, most have undergone receptor editing. The V kappa 4/5H L chain appears to be one of the few L chains that can support differentiation to the mature B-2 cell stage, providing an explanation for its dominance among VH12 B cells in the spleen. Once cells reach this stage, those that bind PtC are induced to differentiate to B-1. Thus, through selection at multiple differentiative stages and the induction of extensive secondary V kappa rearrangement and receptor editing, VH12 B cell differentiation is focused toward specificity for PtC and selection to the B-1 subset.
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Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Clarke
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D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000235:genetics / Q000276:immunology*; D000918:Antibody Specificity; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation; D019070:Cell Lineage; D002469:Cell Separation; D017637:Clonal Deletion; D005434:Flow Cytometry; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D005803:Genes, Immunoglobulin; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D008081:Liposomes / Q000737:chemistry / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D018448:Models, Immunological; D010713:Phosphatidylcholines / Q000276:immunology*; D013154:Spleen / Q000166:cytology* / Q000276:immunology
D017152:Antibodies, Antiphospholipid; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D008081:Liposomes; D010713:Phosphatidylcholines