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Cross-reactivity of IgM- and IgG-secreting B cells in murine chronic graft-versus-host reaction.

A chamber ELISpot assay was used to measure the frequency with which in vivo activated B cells secreted cross-reactive antibodies during a chronic graft-versus-host reaction in mice. Both normal (C57BL/10 x DBA/2)F1 mice and F1 recipients of syngeneic spleen cells (SynF1) expressed repertoires in which 13-17% of IgM and 3-5% of IgG-secreting cells were cross-reactive. By comparison, 43-55% of IgM and 9-40% of IgG-secreting cells from F1 recipients of parental DBA/2 spleen cells (GVHF1) were cross-reactive (P < 0.01, GVHF1 versus F1 or SynF1). The cross-reactivity of the GVHF1 IgM secreting cells remained elevated for > 2 months following cell transfer. In contrast, the cross-reactivity of IgG-secreting cells, which was significantly high at Week 3 post-transfer, declined to nearly normal levels by Week 9. These findings demonstrate that cross-reactive B cells constitute an abnormally large fraction of the repertoire expressed by mice with chronic GVHR in a period when B cell hyperstimulation was occurring.