Affiliation:
1. Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037
Abstract
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 T1→MZ 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.
Publisher
Rockefeller University Press
Subject
Immunology,Immunology and Allergy
Cited by
74 articles.
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