B Cell Immunity in Solid Organ Transplantation

Abstract

The contribution of B cells to alloimmune responses is gradually being understood in more detail. We now know that B cells can perpetuate alloimmune responses in multiple ways: (i) differentiation into antibody-producing plasma cells; (ii) sustaining long-term humoral immune memory; (iii) serving as antigen-presenting cells; (iv) organizing the formation of tertiary lymphoid organs; and (v) secreting pro- as well as anti-inflammatory cytokines. The cross-talk between B cells and T cells in the course of immune responses forms the basis of these diverse functions. In the setting of organ transplantation, focus has gradually shifted from T cells to B cells, with an increased notion that B cells are more than mere precursors of antibody-producing plasma cells. In this review, we discuss the various roles of B cells in the generation of alloimmune responses beyond antibody production, as well as possibilities to specifically interfere with B cell activation.

Keywords: HLA; antigen presentation; cognate T–B interactions; donor-specific antibodies; memory B cells; rejection.

Figure 1

Reciprocal interactions between T cells and B cells. Following B cell receptor-mediated uptake of protein antigens, activated B cells process and present antigenic peptides in the context of major histocompatibility complex (MHC) class II on their surface to cognate T cells that recognize the MHC–peptide complex through their T cell receptor. Ligation of CD40 ligand and CD28 on T cells to CD40 and CD80/86 on B cells, as well as production of several cytokines enable differentiation of both B cells and T cells into effector and memory subsets. While B cells can become isotype-switched antibody-producing plasma cells and memory B cells, T cells can become activated as effectors or differentiate into memory T cells to sustain cellular immune responses.