B-CELL FUNCTION IN MICE TRANSGENIC FOR MCTLA4-H-GAMMA-1 - LACK OF GERMINAL-CENTERS CORRELATED WITH POOR AFFINITY MATURATION AND CLASS SWITCHING DESPITE NORMAL PRIMING OF CD4(-CELLS() T)

This report outlines the B cell phenotype of transgenic mice that over expresses the mouse CTLA-4-human gamma 1 (mCTLA4-H gamma 1) protein. D espite the fact that these mice prime CD4(+) T cells (Ronchese, F., B. Housemann, S. Hubele, and P. Lane. 1994. J. Exp. Med. 179:809), antib ody responses to T-dependent antigens are severely impaired. In contra st, T-independent responses are normal which suggests mCTLA4-H gamma 1 does not act directly on B cells, but acts indirectly by impairing T cell help. The impaired antibody defect is associated with impaired cl ass switching, with low total immunoglobulin (Ig)G and antigen-specifi c IgG responses, and an absence of germinal center formation in spleen and lymph nodes but not gut-associated tissues. The defective germina l center formation is associated with a reduction in the degree of som atic mutation in hybridomas made from transgenic mice in comparison wi th those made from normal mice. It seems likely that mCTLA4-H gamma 1 exerts its effect by blocking an interaction between T and B cells tha t induce T cell help for B cells.