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Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037

CORRESPONDENCE Ann J. Feeney: feeney{at}scripps.edu

Marginal zone (MZ) B cells resemble fetally derived B1 B cells in their innate-like rapid responses to bacterial pathogens, but the basis for this is unknown. We report that the MZ is enriched in "fetal-type" B cell receptors lacking N regions (N^–). Mixed bone marrow (BM) chimeras, made with adult terminal deoxynucleotidyl transferase (TdT)^+/+ and TdT^–/– donor cells, demonstrate preferential repertoire-based selection of N^– B cells into the MZ. Reconstitution of irradiated mice with adult TdT^+/+ BM reveals that the MZ can replenish N^– B cells in adult life via repertoire-based selection and suggest the possibility of a TdT-deficient precursor population in the adult BM. The mixed chimera data also suggest repertoire-based bifurcations into distinct BM and splenic maturation pathways, with mature "recirculating" BM B cells showing a very strong preference for N⁺ complementarity-determining region (CDR) 3 compared with follicular B cells. Because the T1 and MZ compartments are both the most enriched for N^– H-CDR3, we propose a novel direct T1MZ pathway and identify a potential T1–MZ precursor intermediate. We demonstrate progressive but discontinuous repertoire-based selection throughout B cell development supporting multiple branchpoints and pathways in B cell development. Multiple differentiation routes leading to MZ development may contribute to the reported functional heterogeneity of the MZ compartment.

© 2008 Carey et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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