The IgG2a/IgA Produced by the Murine T560 B Lymphoma that Arose During a Graft-Versus-Host Reaction is Polyreactive and Somatically Mutated

Abstract

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 (BIO ± B10.H2aH4bpWts) F, hybrid mouse that had been injected with parental B10.H2aH4h 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 JhI, and by a Vk gene of the Vk 4/5 group juxtaposed to Jkl. Both Vh and Vk are heavily mutated. The IgA binds to polystyrene, top-azophenyl-phosphorylcholine (PC)-conjugated keyhole limpet hemocyanin (KLH) (PC-KLH), to 2,4,6 trinitrophenylated (TNP)-KLH and to human TNF-α but not to KLH, human TNF-a, 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.

Key Words:

• GVH
• Polyreactivity
• Mutation
• Somatic selection
• Isotypc switching
• B lymphoma