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Multiple Levels of Selection Responsive to Immunoglobulin Light Chain and Heavy Chain Structures Impede the Development of Dµ-Expressing B Cells¹

The School of Graduate Studies, Program in Molecular and Cellular Biology, and The Department of Microbiology and Immunology and the Morse Institute for Molecular Genetics, State University of New York–Downstate Medical Center at Brooklyn, Brooklyn, NY 11203

The truncated/V_H-less mouse H chain Dµ forms precursor B cell receptors with the surrogate L chain complex that promotes allelic exclusion but not other aspects of pre-B cell development, causing most progenitor B cells expressing this H chain to be eliminated at the pre-B cell checkpoint. However, there is evidence that Dµ-1 complexes can be made and are positively selected during fetal life but cannot sustain adult B lymphopoiesis. How surrogate and conventional L chains interpret Dµ’s unusual structure and how that affects signaling outcome are unclear. Using nonlymphoid and primary mouse B cells, we show that secretion-competent 1 L chains could associate with both full-length H chains and Dµ, whereas secretion-incompetent 1 L chains could only do so with full-length H chains. In contrast, Dµ could not form receptors with a panel of L chains irrespective of their secretion properties. This was due to an incompatibility of Dµ with the -joining and constant regions. Finally, the Dµ-1 receptor was less active than the full-length mouse µ-1 receptor in promoting growth under conditions of limiting IL-7. Thus, multiple receptor-dependent mechanisms operating at all stages of B cell development limit the contribution of B cells with Dµ H chain alleles to the repertoire.

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 Research Project Grant 00-269-01-LBC from the American Cancer Society, the New York City Council Speaker’s Fund of the New York Academy of Medicine (C.A.J.R.), and the State University of New York.

² Current address: Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65212.

³ Address correspondence and reprint requests to Dr. Christopher Roman, State University of New York-Downstate Medical Center at Brooklyn, 450 Clarkson Avenue Box 44, Brooklyn, NY11203. E-mail address: Christopher.Roman{at}Downstate.edu

⁴ Abbreviations used in this paper: preBCR, precursor B cell receptor; ER, endoplasmic reticulum; HEK, human embryonic kidney; IRES, internal ribosomal entry site; pre-B, precursor B; pro-B, progenitor B; RF2, reading frame 2; SLC, surrogate light chain; UR, unique region.