Exceptionally long CDR3H region with multiple cysteine residues in functional bovine IgM antibodies

We analyzed VDJ and VJ rearrangements in IgM-secreting B lymphocytes from a cow infected with bovine leukemia virus (BLV). BLV causes expansion of CD5 (+) and IgM(+) B lymphocytes regardless of antigen specificity. The data sh owed that single point mutations contribute to the diversification of IgM a ntibodies. The most striking observation, however, is that approximately 9% of the VDJ rearrangement in IgM-secreting B cells encode an exceptionally long third complementarity-determining region of the heavy chain (CDR3H; 56 to61 amino acids) with multiple cysteine residues. Such an exceptionally l ong CDR3H is the first ever to be documented for an antibody in a species. These VDJ rearrangements encode functional IgM antibodies as some of these show polyspecific reactivity. The presence of even-numbered cysteine residu es in the GDR3H may provide hitherto unknown configurational ability to the antigen combining site via intra-CDR3H disulfide bridging. In addition, th e VDJ rearrangements encoding exceptionally long CDR3H paired with either n ovel V(lambda)1 or V(x)1x genes, earlier noted not to be expressed. Overall , these experiments provide evidence that: somatic hypermutations and gener ation of an exceptionally long CDR3H contribute to the diversification of I gM antibodies in cattle.