CD40-independent help by memory CD4 T cells induces pathogenic alloantibody but does not lead to long-lasting humoral immunity.

ABSTRACT: CD40/CD154 interactions are essential for productive antibody responses to T-dependent antigens. Memory CD4 T cells express accelerated helper functions and are less dependent on costimulation when compared with naïve T cells. Here, we report that donor-reactive memory CD4 T cells can deliver help to CD40-deficient B cells and induce high titers of IgG alloantibodies that contribute to heart allograft rejection in CD40-/- heart recipients. While cognate interactions between memory helper T and B cells are crucial for CD40-independent help, this process is not accompanied by germinal center formation and occurs despite inducible costimulatory blockade. Consistent with the extrafollicular nature of T/B cell interactions, CD40-independent help fails to maintain stable levels of serum alloanti

SUBMITTER: Rabant M 

PROVIDER: S-EPMC4019209 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature