Rheumatoid factors and secondary immune responses in the mouse. II. Incidence, kinetics and induction mechanisms.

Production of IgM rheumatoid factor (RF) during secondary immune responses was studied in normal mouse strains by measuring RF synthesis in spleen cell cultures. A considerable, although transient, RF response was observed in BALB/c and C57BL/6 mice immunized and i.v. boosted with various protein antigens and with sheep erythrocytes. With most antigens, RF production equalled or exceeded that of antigen-specific IgM, but it peaked and subsided earlier. No RF production was detected when either priming or boosting was omitted. The isotypic specificity of RF depended upon the antigens used for immunization: all proteins tested stimulated the synthesis of RF specific for IgG1, whereas sheep erythrocytes induced both IgG1- and IgG2a-specific RF. Reconstitution experiments of irradiated naïve C57BL/6 mice with various combinations of syngeneic antibody against human transferrin and primed or unprimed spleen cells indicated that important RF responses could be induced only when antigen was injected into mice that had received both antibody and immune spleen cells.