POLYCLONAL B-CELL ACTIVATION ARISES FROM DIFFERENT MECHANISMS IN LUPUS-PRONE (NZB X NZW)F1 AND MRL MPJ-LPR LPR MICE/

The polyclonal B cell activation is the earliest and most common immun ologic abnormality in lupus-prone mice. However, its cellular mechanis m(s) has not been well defined. To determine the contribution of CD4T cells in this immunologic abnormality, we have depleted CD4+ T cells in lupus-prone (NZB X NZW)F1 and MRL/MpJ-lpr/lpr mice by treating the m with anti-CD4 mAb from birth and determined the development of IgM a nd IgG polyclonal antibody formation. our results indicate that first, different mechanisms control the development of IgM polyclonal B cell activation in these two autoimmune mice; in (NZB X NZW)F1 mice, IgM p olyclonal B cell activation is likely to be a result of an intrinsic B cell defect, whereas CD4+ T cells seem to be responsible for this imm unologic abnormality in MRL/MpJ-lpr/lpr mice. Second, the increased pr oduction of IgG antibodies, including the IgG3 subclass, was totally r egulated by CD4+ T cells in both autoimmune mice. Because IgG3 antibod ies can be highly nephritogenic, independent of their immunologic spec ificities, which is the result of the antibodies' cryoglobulin activit y, the active role of CD4+ T cells in the production of IgG3 antibodie s in lupus-prone autoimmune mice further strengthens the implication o f CD4+ T cells in murine systemic lupus erythematosus.