Highly preferential VH-VL pairing in normal B cells results in antigen-independent selection of the available repertoire.
The aim of this work was to analyze the probabilities of combined expression of the various polymorphic forms of two well-defined VH and VK segments. The availability of two monoclonal antibodies specific, respectively, for the VHT15 and VK21 D-E gene products allowed us to study, both in the selected and in the preimmune repertoire, the expression of VHT15-VK21 D-E pairs in several mouse strains. Our data establish, first, that even before antigen encounters B cells, clones utilize a highly biased repertoire of VH-VL combinations and, secondly, that the level of productive VH-VL pairing depends primarily on the "allelic" form of the relevant VH and VK genes. Furthermore, clonal analysis revealed that this asymmetry in Ig gene expression affects a large proportion of newly arising B cells. Together, these studies demand reconsideration of the current estimates of the available antibody repertoire size, and provide new insights for our understanding of the phenomenon of clonal dominance.
D000483:Alleles; D000818:Animals; D000911:Antibodies, Monoclonal; D000916:Antibody Diversity; D001402:B-Lymphocytes / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007130:Immunoglobulin Idiotypes / Q000032:analysis; D007147:Immunoglobulin Light Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics / Q000276:immunology; D011336:Probability
D000911:Antibodies, Monoclonal; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region