B cell antigen receptor specificity and surface density together determine B-1 versus B-2 cell development.
Mice expressing the immunoglobulin (Ig) heavy (H) chain variable (V) region from a rearranged V(H)12 gene inserted into the IgH locus generate predominantly B-1 cells, whereas expression of two other V(H) region transgenes (V(H)B1-8 and V(H)glD42) leads to the almost exclusive generation of conventional, or B-2, cells. To determine the developmental potential of B cells bearing two distinct B cell antigen receptors (BCRs), one favoring B-1 and the other favoring B-2 cell development, we crossed V(H)12 insertion mice with mice bearing either V(H)B1-8 or V(H)glD42. B cells coexpressing V(H)12 and one of the other V(H) genes are readily detected in the double IgH insertion mice, and are of the B-2 phenotype. In mice coexpressing V(H)12, V(H)B1-8 and a transgenic kappa chain able to pair with both H chains, double H chain-expressing B-2 cells, and B-1 cells that have lost V(H)B1-8 are generated, whereas V(H)B1-8 single producers are undetectable. These data suggest that B-1 but not B-2 cells are selected by antigenic stimuli in whose delivery BCR specificity and surface density are of critical importance.
Lam
K P
KP
Institute of Molecular and Cell Biology, The National University of Singapore, Singapore 117609, Republic of Singapore. mcblamkp@imcb.nus.edu.sg
Rajewsky
K
K
D000483:Alleles; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D018390:Gene Targeting; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D016254:Mutagenesis, Insertional; D010529:Peritoneal Cavity / Q000166:cytology; D016364:Reading Frames; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D011947:Receptors, Antigen, B-Cell