Truncation of the μ heavy chain alters BCR signalling and allows recruitment of CD5+ B cells

Open Access
Publisher Website
Google Scholar
Abstract
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.