CO-TRANSFER OF B-CELLS CONVERTS RESISTANCE INTO SUSCEPTIBILITY IN T-CELL-RECONSTITUTED, LEISHMANIA MAJOR-RESISTANT C.B-17 SCID MICE BY A NONCOGNATE MECHANISM

Resistance to infection of mice with Leishmania major parasites is dep endent on the production of IFN-gamma by CD4(+) T helper cells, C.B-17 acid mice, lacking both T and B cells, succumb very quickly to the in fection, but develop resistance if reconstituted with appropriate numb ers of T cells from BALB/c mice, In this model, we studied the role of B cells with regard to their ability to influence disease outcome and to function as antigen-presenting cells for T cells, For this purpose , we reconstituted scid mice (H-2(d)) with either T cells or with T an d B cells obtained from (BALB/c x BALB.B)F-1 mice (H-2(d x b)), and in fected them with L. major parasites 1 day after reconstitution, Mice r econstituted with T cells alone cured the disease, whereas additional B cell reconstitution led to susceptibility, Healing was associated wi th a predominant T(h)1-type response, In all mice, L. major-specific T cell proliferation was restricted to the MHC phenotype of the recipie nt (H-2(d)) but not to that of the donor (H-2(d x b)), indicating that there was no detectable contribution of donor B cells in the priming of a T cell response, Furthermore, a cells, when purified from infecte d BALB/c mice, were unable to stimulate a L. major-specific CD4(+) T c ell clone (L1/1) without addition of exogenous antigen, in contrast to macrophages from the same animal, These data suggest that B cells, in vivo, do not carry L. major antigen in a form capable of activating s pecific CD4(+) T cells, Therefore, B cells promote disease by means ot her than cognate interaction with CD4(+) T cells.