Cognate T cell help for B cell activation

The CD40 ligand (CD40L) expressed by activated T cells is a 33 kDa type II membrane glycoprotein with sequence homology to tumor necrosis factor. T cells activated through TCR ligation transiently express on their surface CD40L, which interacts with CD40 expressed on B cells to deliver signals for B cell activation and proliferation. Signaling through CD40 in combination with T cell-derived cytokines such as IL-4 and IL-5 in mice leads to B cell differentiation accompanied by antibody secretion and Ig isotype switching. The CD40-CD40L interaction is also important for other B cell functions including the formation of germinal centers and the induction of memory B cells. The physiological significance of the CD40-CD40L interaction in vivo has become evident from the observation of patients with X-linked hyper-IgM syndrome, who have mutations in the gene encoding CD40L and are therefore unable to express functional CD40L on their T cells. These patients fail to produce Ig of isotypes other than IgM in response to antigen challenge and also lack germinal centers in their secondary lymphoid organs.

The cognate interaction of B and T cells triggers the engagement of many other accessory molecules on both cells, which serve to stabilize the B-T conjugation and to coordinate the responses of the interacting cells. They include B7-1 (CD80), B7-2 (CD86), CTLA-4, LFA-1 (CD1 la/18), LFA-2 (CD2), LFA-3 (CD58), ICAM-1 (CD54), VCAM (CD106) and VLA-4 (CD49d/29). The B7-1/B7-2 expressed on B cells interacts with the CD28 expressed on T cells to deliver a costimulatory signal to TCR-stimu-lated T cells, which then become fully activated to produce cytokines. T cell-derived cytokines such as IL-2, IL-4, IL-5, IL-6, IL-10, IL-13 and interferon y (IFNy) have been shown to enhance B cell activation and proliferation and to be essential costimuli for subsequent B cell differentiation and Ig production.

How To Bolster Your Immune System

How To Bolster Your Immune System

All Natural Immune Boosters Proven To Fight Infection, Disease And More. Discover A Natural, Safe Effective Way To Boost Your Immune System Using Ingredients From Your Kitchen Cupboard. The only common sense, no holds barred guide to hit the market today no gimmicks, no pills, just old fashioned common sense remedies to cure colds, influenza, viral infections and more.

Get My Free Audio Book


Post a comment