Co-transfer of B cells converts resistance into susceptibility in T cell-reconstituted, Leishmania major-resistant C.B-17 scid mice by a non-cognate mechanism.
Resistance to infection of mice with Leishmania major parasites is dependent on the production of IFN-gamma by CD4+ T helper cells. C.B-17 scid mice, lacking both T and B cells, succumb very quickly to the infection, but develop resistance if reconstituted with appropriate numbers 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-2d) with either T cells or with T and B cells obtained from (BALB/c x BALB.B)F1 mice (H-2d x b), and infected them with L. major parasites 1 day after reconstitution. Mice reconstituted with T cells alone cured the disease, whereas additional B cell reconstitution led to susceptibility. Healing was associated with a predominant Th1-type response. In all mice, L. major-specific T cell proliferation was restricted to the MHC phenotype of the recipient (H-2d) but not to that of the donor (H-2d x b), indicating that there was no detectable contribution of donor B cells in the priming of a T cell response. Furthermore, B cells, when purified from infected BALB/c mice, were unable to stimulate a L. major-specific CD4+ T cell 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 specific CD4+ T cells. Therefore, B cells promote disease by means other than cognate interaction with CD4+ T cells.
Hoerauf
A
A
Institute of Clinical Microbiology, University of Erlangen-Nürnberg, Germany.
Röllinghoff
M
M
Solbach
W
W
D000818:Animals; D001402:B-Lymphocytes / Q000637:transplantation*; D004198:Disease Susceptibility; D005260:Female; D007113:Immunity, Innate / Q000276:immunology; D007116:Immunization, Passive / Q000379:methods; D018320:Leishmania major / Q000472:pathogenicity*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D017710:Lymphocyte Transfusion / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D013601:T-Lymphocytes / Q000637:transplantation*