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Intraclonal Competition Inhibits the Formation of High-Affinity Antibody-Secreting Cells¹

Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294

Protective immunity requires a diverse, polyclonal B cell repertoire. We demonstrate that affinity maturation of the humoral response to a hapten is impaired when preexisting clonally restricted cells recognizing the hapten are dominant in the B cell repertoire. B1-8i^+/– mice, which feature a high frequency of B cells with nitrophenyl (NP)-binding specificity, respond to NP-haptenated proteins with the production of NP-specific Abs, but affinity maturation is impaired due to insufficient generation of high-affinity Ab-producing cells. We manipulated the frequency of NP-specific B cells by adoptive transfer of B1-8 B cells into naive, wild-type recipients. Remarkably, when 10⁴ B1-8 B cells were transferred, these cells supported efficient affinity maturation and plasma cell differentiation. In contrast, when 10⁶ B1-8 cells were transferred, affinity maturation did not occur. These data indicate that restricting the frequency of clonally related B cells is required to support affinity maturation.

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 National Institute of Allergy and Infectious Diseases—National Institutes of Health Training Grant T32 AI007493 (to T.L.L.).

² Current address: Department of Microbiology & Immunology, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322.

³ Address correspondence and reprint requests to Dr. David D. Chaplin, Department of Microbiology, University of Alabama at Birmingham, 845 19th Street South, Birmingham, AL 35294. E-mail address: dchaplin{at}uab.edu

⁴ Abbreviations used in this paper: SHM, somatic hypermutation; ASC, Ab-secreting cells; BM, bone marrow; HC, H chain; KLH, keyhole limpet hemocyanin; LC, L chain; NP, (4-hydroxy-3-nitrophenyl)acetyl; CSR, class switch recombination; GC, germinal center; WT, wild type; MHC II, MHC class II; NIP, 4-hydroxy-3-iodo-5-nitrophenyl acetyl; R:S, replacement: silent; VLP, virus-like particle.