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¹ Department of Pediatrics and ² Department of Immunology, University of Washington School of Medicine, Seattle, WA 98195
³ Department of Microbiology and Immunology, Albert Einstein College of Medicine Bronx, NY 10461

CORRESPONDENCE David J. Rawlings:drawling{at}u.washington.edu

We have characterized a distinct, late transitional B cell subset, CD21^int transitional 2 (T2) B cells. In contrast to early transitional B cells, CD21^int T2 B cells exhibit augmented responses to a range of potential microenvironmental stimuli. Adoptive transfer studies demonstrate that this subset is an immediate precursor of both follicular mature and marginal zone (MZ) B cells. In vivo, a large percentage of CD21^int T2 B cells has entered the cell cycle, and the cycling subpopulation exhibits further augmentation in mitogenic responses and B cell-activating factor of the TNF family (BAFF) receptor expression. Consistent with these features, CD21^int T2 cells exhibit preferential responses to BAFF-facilitated homeostatic signals in vivo. In addition, we demonstrate that M167 B cell receptor (BCR) idiotypic-specific B cells are first selected within the cycling CD21^int T2 population, ultimately leading to preferential enrichment of these cells within the MZ B cell compartment. These data, in association with the coordinate role for BAFF and microenvironmental cues in determining the mature BCR repertoire, imply that this subset functions as a unique selection point in peripheral B cell development.

Abbreviations used: AAD, amino actinomycin D; BAFF, B cell-activating factor of the TNF family; BAFF-R, BAFF receptor; BCR, B cell receptor; FM, follicular mature; HP, homeostatic proliferation; KREC, -deleting recombination excision circle; MZ, marginal zone; MZP, MZ precursor; PC, phosphorylcholine; TLR, Toll-like receptor.

A. Meyer-Bahlburg and S.F. Andrews contributed equally to this paper.

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