Figure 4.

Peptide-Independent Recognition of the B Cell MHC Class II Complex by Donor CD4 T Cells Promotes Plasma Cell Differentiation but Requires Concurrent BCR Ligation

(A) Seven days after transfer of bm12 CD4 T cells into B6 hosts, flow cytometric analysis of the splenic CD19^+ve B cell compartment demonstrates global upregulation of MHC class II expression, which is not evident upon transfer of syngeneic B6 CD4 T cells.

(B and C) Whereas intravenous transfer of Tcrbd^−/− B6 mice with bm12 CD4 T cells provoked anti-nuclear IgG autoantibody (B), only those mice simultaneously immunized subcutaneously with ovalbumin (OVA) protein developed anti-OVA IgG (C).

(D and E) Similarly, intravenous transfer of Tcrbd^−/− B6 mice with either purified bm12 CD4 T cells or bm12 CD4 T cells that expressed H-2K^d transgene (bm12.K^d) provoked anti-nuclear IgG autoantibody (D), but anti-K^d IgG alloantibody was only generated in Tcrbd^−/− B6 mice that received bm12.K^d CD4 T cells (E).

(F and G) Adoptive transfer of purified bm12.K^d CD4 T cells into T cell-deficient Tcrbd^−/− bm12 recipients of a BALB/c heart allograft confirmed not only that bm12 and bm12.K^d CD4 T cells can provide help for generating humoral alloimmunity, as determined by flow cytometric detection of bound test sera to target BALB/c BMDCs (F) but also that bm12.K^d CD4 T cells are tolerant of self (I-A^bm12)-restricted H-2K^d peptide and do not provide help for generating anti-K^d IgG alloantibody (G).

^∗p < 0.05, ^∗∗p < 0.01, and ^∗∗∗p < 0.001 (Mann-Whitney test in C and F; two-way ANOVA in E and G). Data are representative of three independent experiments (A; n = 6 mice per group) or one experiment (B–G; mean and SEM of n = 4 mice per group).