Repertoire‐based selection during B cell development in polyclonal mice

Marginal zone (MZ) B cells resemble fetally‐derived B1 B cells in their innate‐like rapid responses to blood‐borne pathogens but the basis for this is unknown. H‐CDR3 sequence analysis reveals that 20% of MZ B cells in C57BL/6 mice possess fetally‐derived and fetal‐type BCR which lack N regions (N − ). Using bone marrow chimeras, with adult TdT +/+ and TdT −/− donor cells, we demonstrate preferential repertoire‐based selection of N − fetal‐type B cells into the MZ, indicating a functional importance for these specificities. Furthermore, selection events in bone marrow and splenic transitional compartments show differential selection for these N + and N − H‐CDR3 repertoires, with the N − repertoire being more enriched in Ig λ expression. Entry into the splenic T1 compartment favors the N − repertoire. In contrast, the T3 population, which is enriched in anergic and autoreactive B cells, preferentially selects the adult‐type, N‐region containing, and Ig κ repertoires. Our data suggest repertoire‐based bifurcations early and late in B cell differentiation and suggest novel differentiation pathways for MZ B cell development, based on H‐CDR3 and light chain differences.