Analysis of marginal zone B cell development in the mouse with limited B cell diversity: role of the antigen receptor signals in the recruitment of B cells to the marginal zone.
The quasimonoclonal (QM) mouse provides an intelligible model to analyze the B cell selection as the competition between two major 4-hydroxy-3-nitrophenylacetyl-specific B cell populations whose BCR are comprised of the knockin V(H)17.2.25 (V(H)T)-encoded H chain and the lambda1 or lambda2 L chain. In this study, we show the QM system is useful to examine how BCR signals guide a subset of B cells to the marginal zone (MZ). Compared with the control C57BL/6 mice, the QM mice had approximately 2.7-fold increased number of B cells exhibiting the MZ B cell phenotype and a larger MZ area in the spleen. Interestingly, V(H)T/lambda2 B cells significantly predominated over V(H)T/lambda1 B cells in MZ-(V(H)T/lambda1:V(H)T/lambda2 approximately 3:7) and transitional 2-B cell subsets, while these two populations were comparable in immature, transitional 1, and mature counterparts. Thus, the biased use of lambda2 in the MZ B cells may be the result of selection in the periphery. The enlargement of MZ B cell compartment and the preferred recruitment of the V(H)T/lambda2 B cells were further augmented by doubling the V(H)T gene, but dampened by the dysfunction of Bruton's tyrosine kinase, suggesting a positive role of BCR signaling in this selection. Comparison of Ag specificity between V(H)T/lambda1 and V(H)T/lambda2 IgM mAbs revealed a polyreactive nature of the V(H)T/lambda2 BCR, including the reactivity with ssDNA. Taken together, it is suggested that polyreactivity (including self-reactivity) of BCR is crucial in driving B cells to differentiate into the MZ phenotype.
Kanayama
Naoki
N
Department of Bioscience and Biotechnology, Faculty of Engineering, Okayama University, Tsushima-Naka, Okayama, Japan.
Cascalho
Marilia
M
Ohmori
Hitoshi
H
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D006241:Haptens / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis; D007146:Immunoglobulin lambda-Chains / Q000096:biosynthesis; D016130:Immunophenotyping; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009596:Nitrophenols / Q000276:immunology; D010648:Phenylacetates; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
D001323:Autoantibodies; D006241:Haptens; D007143:Immunoglobulin Heavy Chains; D007146:Immunoglobulin lambda-Chains; D009596:Nitrophenols; D010648:Phenylacetates; D011947:Receptors, Antigen, B-Cell; C026242:4-hydroxy-5-nitrophenyl acetic acid