The IgG2a/IgA produced by the murine T560 B lymphoma that arose during a graft-versus-host reaction is polyreactive and somatically mutated

In mice undergoing a graft-versus-host (GVH) reaction, donor T cells responding to the host's MHC antigens induce polyclonal activation of the host's B cells and secretion of their antibodies and autoantibodies. T560, a CD5^- B lymphoma that arose in the gut-associated lymphoid tissue (GALT) of a (B10 x B10.H2^aH4^bpWts) F₁ hybrid mouse that had been injected with parental B10.H2^aH4^b splenocytes, is of particular interest because it produces switched, heavily mutated, but, nevertheless, polyreactive immunoglobulin. T560 bears and contains IgG2a but switches to IgA spontaneously. The T560 Ig variable region is encoded by a V186.2-related VH gene, juxtaposed to DFL 16 and JH1, and by a Vκ gene of the Vκ 4/5 group juxtaposed to Jκ1. Both VH and Vκ are heavily mutated. The IgA binds to polystyrene, to p-azophenyl-phosphorylcholine (PC)-conjugated keyhole limpet hemocyanin (KLH) (PC-KLH), to 2,4,6 trinitrophenylated (TNP)-KLH and to human TNF-β but not to KLH, human TNF-α, or any of several other Ags tested. Hapten inhibition experiments indicate that the polystyrene, PC- and TNP-binding sites do not overlap. The switched isotypes and heavy load of somatic mutations found in the T560 IgG2a/IgA suggest that T cell-dependant somatic selection of the T560 precursor B cell may have been superimposed on polyclonal B cell activation originally associated with the GVH.