A brief history of T cell help to B cells

Abstract

In celebration of the 50th anniversary of the discovery of B cells, I take a look back at the history of T cell help to B cells, which was discovered 47 years ago. In addition, I summarize and categorize the distinct molecules that are expressed by CD4(+) T cells that constitute 'help' to B cells, and particularly the molecules expressed by T follicular helper (TFH) cells, which are the specialized providers of help to B cells.

Figure 1. A timeline of discoveries about T cell help to B cells

T cell help to B cells was discovered only a few years after the discovery of B cells. Subsequent discoveries lead to coining of the term T follicular helper (T_FH) cells ~30 years later. BCL-6, B cell lymphoma 6; CXCR5, CXC-chemokine receptor 5; ICOS, inducible T cell co-stimulator; SAP, SLAM-associated protein.

Figure 2. Categories of T cell help to B cells

Help can come in many different forms and can have different consequences for different processes. T follicular helper (T_FH) cells provide seven main forms of T cell help to B cells: signals that promote survival, proliferation, plasma cell differentiation, hypermutation, class-switch recombination, adhesion and chemoattraction (cell migration). For simplicity, only a few examples of factors that are important for each process are shown, although many more molecules are involved in the regulation of the processes. Several of these pathways are reviewed in detail elsewhere^,,. Some molecules have pleiotropic effects, resulting in combinatorial possibilities and functional redundancies between molecules. AID, activation-induced cytidine deaminase; BAFF, B cell-activating factor; BCL, B cell lymphoma; BLIMP1, B lymphocyte-induced maturation protein 1; CD40L, CD40 ligand; CXCL13, CXC-chemokine ligand 13; CXCR5, CXC-chemokine receptor 5; IL, interleukin; MCL1, myeloid cell leukaemia 1; SAP, SLAM-associated protein; SLAMF, signalling lymphocytic activation molecule F; TGFβ, transforming growth factor-β.