Evidence for B cell antigen receptor (BCR)‐driven, BAFF‐facilitated positive selection within a unique population of late transitional B cells

Abstract

In addition to negative selection, several lines of evidence suggest that positive selection may also play an important role in shaping the naïve mature B cell repertoire.We have characterized a late transitional (T2) B cell subset with a distinct phenotypic, functional, and gene expression profile. Adoptive transfer experiments identify this subset as an immediate precursor of both follicular mature (FM) and marginal zone (MZ) B cells. Intriguingly, in contrast to the largely quiescent early transitional (T1) and FM B cells, a high percentage of T2 B cells are actively cycling as demonstrated by cell cycle analysis, measurement of kappa‐deleting recombination excision circles (KRECS) and in vivo BrdU labeling. Proliferation of this subset is BAFF‐dependent, consistent with the highest levels of BAFF‐R expression among all splenic B cells. Finally, M167 BCR idiotypic‐specific B cells are first selected by self‐antigen within this subset leading, ultimately, to preferential enrichment within the MZ compartment.In summary, our data indicate that late transitional B cells represent a bipotent precursor for mature splenic B cells; and can function as a target for BCR‐driven, BAFF‐facilitated homeostatic signaling. These combined findings suggest that this small pool of cells may operate at a previously unknown selection point important for establishment of the mature B repertoire. Funded by NIH 5RO1HD37091