Selection at multiple checkpoints focuses V(H)12 B cell differentiation toward a single B-1 cell specificity.
Phosphatidyl choline (PtC)-specific B cells segregate to the B-1 subset, where they comprise up to 10% of the B-1 repertoire. About half express V(H)12 and Vkappa4/5H and are restricted in V(H)CDR3. We have previously reported that anti-PtC V(H)CDR3 is enriched among V(H)12-expressing cells by selective elimination of pre-B cells. We report here a bias for Vkappa4/5H expression among V(H)12-expressing B cells, even among those that do not bind PtC and are not B-1. This is due in part to an inability of V(H)12 to associate with many light (L) chains but must also be due to a selective advantage in survival or clonal expansion in the periphery for Vkappa4/5H-expressing cells. Thus, the bias for Vkappa4/5H expression is independent of PtC binding, and, as segregation to B-1 occurs after Ig gene expression, it precedes segregation to the B-1 subset. In 6-1 mice, splenic B-1 cells reside in follicles but segregate to follicles distinct from those that contain B-2 cells. These data indicate that selection at multiple developmental checkpoints ensures the co-expression of an anti-PtC V(H)CDR3 and L chain in a high frequency of V(H)12 B cells. This focus toward specificity for PtC facilitates the development of a large anti-PtC B-1 repertoire.
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Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Ye
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J
Arnold
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LW
Clarke
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SH
D000595:Amino Acid Sequence; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D002470:Cell Survival; D022801:Complementarity Determining Regions; D003433:Crosses, Genetic; D005434:Flow Cytometry; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010713:Phosphatidylcholines / Q000276:immunology; D013154:Spleen / Q000276:immunology
D022801:Complementarity Determining Regions; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D010713:Phosphatidylcholines