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 respon ding 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(a)H4(b)pWts) F-1 hybrid mouse that had been injected with pare ntal B10.H2(a)H4(b) splenocytes, is of particular interest because it produ ces switched, heavily mutated, but, nevertheless, polyreactive immunoglobul in. T560 bears and contains IgG2a but switches to IgA spontaneously, The T5 60 Tg variable region is encoded by a V186.2-related VH gene, juxtaposed to DFL 16 and JH1, and by a V kappa gene of the V kappa 4/5 group juxtaposed to J kappa 1. Both VH and V kappa are heavily mutated. The IgA binds to pol ystyrene, to p-azophenyl-phosphorylcholine (PC)-conjugated keyhole Limpet h emocyanin (KLH) (PC-KLH), to 2,4,6 trinitrophenylated (TNP)-KLH and to huma n TNF-beta but not to KLH, human TNF-alpha, or any of several other Ags tes ted, Hapten inhibition experiments indicate that the polystyrene, PC- and T NP-binding sites do not overlap, The switched isotypes and heavy load of so matic mutations found in the T560 IgG2a/IgA suggest that T cell-dependant s omatic selection of the T560 precursor B cell may have been superimposed on polyclonal B cell activation originally associated with the GVH.