HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Palanichamy, A. Articles by Anolik, J. H. Search for Related Content PubMed PubMed Citation Articles by Palanichamy, A. Articles by Anolik, J. H.

Novel Human Transitional B Cell Populations Revealed by B Cell Depletion Therapy¹

Department of Medicine, Division of Clinical Immunology and Rheumatology; University of Rochester Medical Center, Rochester, NY 14642

Transitional cells represent a crucial step in the differentiation and selection of the mature B cell compartment. Human transitional B cells have previously been variably identified based on the high level of expression of CD10, CD24, and CD38 relative to mature B cell populations and are expanded in the peripheral blood following rituximab-induced B cell-depletion at reconstitution. In this study, we take advantage of the gradual acquisition of the ABCB1 transporter during B cell maturation to delineate refined subsets of transitional B cells, including a late transitional B cell subset with a phenotype intermediate between T2 and mature naive. This late transitional subset appears temporally following the T1 and T2 populations in the peripheral compartment after rituximab-induced B cell reconstitution (and is thus termed T3) and is more abundant in normal peripheral blood than T1 and T2 cells. The identity of this subset as a developmental intermediate between early transitional and mature naive B cells was further supported by its ability to differentiate to naive during in vitro culture. Later transitional B cells, including T2 and T3, are found at comparatively increased frequencies in cord blood and spleen but were relatively rare in bone marrow. Additional studies demonstrate that transitional B cells mature across a developmental continuum with gradual up-regulation of mature markers, concomitant loss of immature markers, and increased responsiveness to BCR cross-linking in terms of proliferation, calcium flux, and survival. The characterization of multiple transitional B cell subpopulations provides important insights into human B cell development.

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 in part by National Institutes of Health Grants K08AR048303 and R01AI077674-01A1to J.H.A., the Lupus Foundation of America, the Alliance for Lupus Research, and the Lupus Research Institute, the Lupus Clinical Research Consortium to R.J.L., and Grants R01 AI049660-01A1 and U19 Autoimmunity Center of Excellence AI56390 to I.S.

² Address correspondence and reprint requests to Dr. Jennifer Anolik, University of Rochester School of Medicine, Box 695, 601 Elmwood Avenue, Rochester, NY 14642. E-mail address: jennifer_anolik{at}urmc.rochester.edu

³ Abbreviations used in this paper: BM, bone marrow; SLE, systemic lupus erythematosus; R123, rhodamine 123; BAFF, B cell-activating factor of the TNF family; MFI, mean fluorescence intensity; PB, peripheral blood; GC, germinal center; CB, cord blood; PC, proliferative capacity; MTG, Mitotracker green.