Antigen Dependent B Cell Activation
A key part of the immune system is the production of immunoglobulins (antibodies) by B cells to bind and inactivate specific foreign antigens. The body produces B cells with a wide range of antigen specificities in the immunoglobulin B cell receptor, one antigen specificity per cell. When the B cell receptor immunoglobulin binds antigen, that cell is activated to proliferate and create plasma cells secreting immunoglobulins to bind that specific antigen. B cell activation also creates memory cells with the same antigen specificity that do not actively secrete immunoglobulin but provide for rapid future immune responses to the same antigen.B cells are not activated by antigen on their own, but require interaction with helper CD4+ T cells to become activated and proliferate. The B cell first expresses immunoglobulin on the cell surface as the B cell receptor. If the B cell receptor immunoglobulin binds specific antigen, then the cell internalizes the antigen and presents it to T cells in MHC II, where it is recognized by the T cell receptor. In addition to the interaction between the T cell receptor and the B cell MHC-antigen, T cell interaction with the B cell involves additional positive and negative regulatory signals. CD40 interaction with CD40L and CD28 interaction with CD80 provide positive costimulatory signals that stimulate B cell activation and proliferation. T cell receptor activation induces expression of molecules like the CD40 ligand that modulate the B cell-T cell interaction. The CD40-CD40L interaction induces cytokine production and expression of other genes and alters the fate of the B cell involved in the interaction. If the interaction between CD40 and CD40L is prolonged, the B cell can be induced to become a memory cell rather than a plasma cell. Fas ligand binding to Fas between B and T cells may negatively modulate B cell activation, inducing apoptosis that limits B cell proliferation and activation. Cytokines like IL-2, IL-4 and IL-10 also play an important role in B cell activation.
Contributor: Glenn Croston, PhD.
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