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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 Zone¹

Naoki Kanayama^*, Marilia Cascalho and Hitoshi Ohmori^2,*

^* Department of Bioscience and Biotechnology, Faculty of Engineering, Okayama University, Tsushima-Naka, Okayama, Japan; and Department of Surgery and Immunology, Mayo Clinic, Rochester, MN 55905

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_H17.2.25 (V_HT)-encoded H chain and the 1 or 2 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 2.7-fold increased number of B cells exhibiting the MZ B cell phenotype and a larger MZ area in the spleen. Interestingly, V_HT/2 B cells significantly predominated over V_HT/1 B cells in MZ-(V_HT/1:V_HT/2 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 2 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_HT/2 B cells were further augmented by doubling the V_HT 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_HT/1 and V_HT/2 IgM mAbs revealed a polyreactive nature of the V_HT/2 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.

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