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The Recirculating B Cell Pool Contains Two Functionally Distinct, Long-Lived, Posttransitional, Follicular B Cell Populations¹

Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129

Disparate models for the development of peripheral B cells may reflect significant heterogeneity in recirculating long-lived B cells that have not been previously accounted for. We show in this study that the murine recirculating B cell pool contains two distinct, long-lived, posttransitional, follicular B cell populations. Follicular Type I IgM^low B cells require Ag-derived and Btk-dependent signals for their development and make up the majority of cells in the recirculating follicular B cell pool. Follicular type II B cells do not require Btk- or Notch-2-derived signals, make up about a third of the long-lived recirculating B cell pool, and can develop in the absence of Ag. These two follicular populations exhibit differences in basal tyrosine phosphorylation and in BCR-induced proliferation, suggesting that they may represent functionally distinct populations of long-lived recirculating B cells.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Grants AI06493 and CA102793 from the National Institutes of Health.

² Address correspondence and reprint requests to Dr. Shiv Pillai, MGH Cancer Center, Building 149, 13th Street, Charlestown, MA 02129. E-mail address: pillai{at}helix.mgh.harvard.edu

³ Abbreviations used in this paper: NF/T1, newly formed or transitional type 1; T2, transitional type 2; T3, transitional type 3; MZ, marginal zone; MZP, MZ precursor; APC, allophycocyanin; HEL, hen egg lysozyme; SA, streptavidin; BrdU, bromodeoxyuridine; FO II, follicular type II; FO I, follicular type I.

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