Question

CD40 is: (Select ALL that apply)

a. Involved in isotype switching of a B-cell

b. Expressed only when a B-cell is infected

c. A part of the second signal required for T-cell dependent activation of a B-cell

d. Capable of interacting with the T-cell receptor

e. Necessary for antigen recognition by an antibody

Answer 1

In the initiation of an adaptive immune response, multiple signals are necessary. A primary signal is the engagement of the T-cell antigen receptor (TCR), with polypeptides derived from a protein presented in the context of major histocompatability complex II (MHC II) on the surface of antigen-presenting cells (APCs) and the binding of native antigen to a cognate B-cell receptor (BCR) complex expressed by B cells. Subsequent secondary signals involve the engagement of costimulatory molecules expressed as receptor and ligand pairs between T cells and APCs and between B cells and T cells, with CD40 ligand (CD40L) expressed by activated T cells engaging CD40 expressed by B cells and APCs. Other accessory signals are necessary: the secretion of cytokines functioning to further enhance, modify, and skew the responding effector cells. Although T-cell priming and B-cell activation can occur in absence of CD40 signals, many cellular and immune functions are defective in the absence of this interaction, underscoring the importance of this ligand/receptor pair in the development of adaptive immunity.

Overall, the impact of CD40 signaling ‘licenses’ DCs (dendritic cells) to mature and achieve all of the necessary characteristics to effectively trigger T-cell activation and differentiation. CD40 signaling of B cells promotes germinal center (GC) formation, immunoglobulin (Ig) isotype switching, somatic hypermutation (SHM) of the Ig to enhance affinity for antigen, and finally the formation of long-lived plasma cells and memory B cells. Moreover, it has been shown that the CD40 pathway is essential for the survival of many cell types including GC B cells, DCs, and endothelial cells under normal and inflammatory conditions (15). In a pathogenic setting, the deregulation of CD40 signaling has been observed in multiple autoimmunity diseases. Together, this breadth of functions for CD40 underline the importance this receptor contains during the generation of an acquired immune response.