Polyclonal B cell activation and antigen-specific stimulation in mice with chronic graft-versus-host reaction

Primary chronic graft-versus-host reaction (GVHR) was induced in (C57BL/10 x DBA/2)F1 (BDF1) mice via the transfer of parental DBA/2 derived lymphocytes. A significant increase in the absolute number of IgM- and IgG-secreting cells was found in recipient BDF1 mice at 3 weeks post-transfer. The increase included B cells reactive with both self- and non-self-antigens, without being skewed toward the production of autoantibodies. Later in the disease process (approximately 6-8 weeks post-transfer), we detected an increased number of B cells that secreted antibodies reactive with a select subset of autoantigens in about 30% of BDF1 recipients (3 of 9 mice). These findings suggest that not only antigen-specific stimulation, which was detected in a late stage, but also initial polyclonal activation may account for chronic GVHR.