International Immunology, Vol. 13, No. 12, 1489-1499,
December 2001
© 2001 Japanese Society for Immunology
Truncation of the µ heavy chain alters BCR signalling and allows recruitment of CD5+ B cells
Laboratory of Developmental Immunology, The Babraham Institute, Babraham, Cambridge CB2 4AT, UK
Correspondence to: M. Brüggemann
Ig are multifunctional molecules with distinct properties assigned to individual domains. To assess the importance of IgM domain assembly in B cell development we generated two transgenic mouse lines with truncated µH chains by homologous integration of the neomycin resistance gene (neor) into exons Cµ1 and Cµ2. Upon DNA rearrangement shortened µH chain transcripts, VH–D–JH–Cµ3–Cµ4, are produced independent of the transcriptional orientation and termination signals provided by neor. The truncated µH chain of ~52 kDa associates non-covalently with the L chain to form a monovalent HL heterodimer. Surface IgM is assembled into a defective BCR complex which has lost important signalling capacity. In immunizations with T-dependent and T-independent antigens, specific IgM antibodies cannot be detected, whilst IgG responses remain normal. B cell development in the bone marrow is characterized by an increase in early B cells, but a decrease of B220+ cells from the stage when µH chain rearrangement is completed. The peritoneal lymphocyte population has elevated levels of CD5+ B cells and their expansion may be the result of a negative feedback mechanism. The results show that antigenic stimulation is compromised by truncated monovalent IgM and that this deficit in stimulation leads to reduced levels of conventional B-2 lymphocytes, but dramatically increased levels of B-1 cells.
Keywords: µH chain truncation, BCR signalling, B-1 cell expansion, monovalent IgM, CD5+ B cells
Transmitting editor: E. Simpson
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