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Blood, 1 February 2005, Vol. 105, No. 3, pp. 1121-1126.
Prepublished online as a Blood First Edition Paper on October 12, 2004; DOI 10.1182/blood-2004-06-2344.
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IMMUNOBIOLOGY
FcRH1: an activation coreceptor on human B cells
Chuen-Miin Leu,
Randall S. Davis,
Lanier A. Gartland,
W. David Fine, and
Max D. Cooper
From the Division of Developmental and Clinical Immunology, University of Alabama at Birmingham, Birmingham; the Division of Hematology/Oncology, University of Alabama at Birmingham, Birmingham; the Department of Medicine, University of Alabama at Birmingham, Birmingham; the Department of Pathology, University of Alabama at Birmingham, Birmingham; the Department of Pediatrics, University of Alabama at Birmingham, Birmingham; the Department of Microbiology, University of Alabama at Birmingham, Birmingham; and the Howard Hughes Medical Institute, University of Alabama at Birmingham, Birmingham.
B-cell activation and differentiation is regulated through the coordinated function of a dynamic array of cell surface receptors. At different stages in their differentiation, human B cells may express one or more members of a large family of immunoglobulin Fc receptor homologs (FcRH) with regulatory potential. Among these newly identified transmembrane molecules, FcRH1 is unique in having 2 immunoreceptor tyrosine-based activation motif (ITAM)–like motifs in its intracellular domain. Here we used the Fab fragments of new monoclonal anti-FcRH1 antibodies and mRNA analysis to evaluate FcRH1 expression and function during B-cell differentiation. FcRH1 expression begins in pre-B cells, reaches peak levels on naive B cells, and is down-regulated after B cells are activated to begin to form germinal centers. This FcRH1 down-regulation coincides with dramatic enlargement of the pre-germinal center cells, cell cycle entry, and other overt signs of activation that include CD80 and CD86 up-regulation and immunoglobulin D (IgD) down-regulation. In vitro analysis indicates that ligation of FcRH1 leads to its tyrosine phosphorylation and to modest B-cell activation and proliferation. Concomitant FcRH1 ligation enhances B-cell antigen receptor (BCR)–induced Ca2+ mobilization and proliferation. FcRH1 thus has the potential to serve as an activating coreceptor on B cells.
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