B Cell Activation, Tolerance and Antigen-presenting Function

Current Opinion in Immunology 1995, 7:121-129

By Philip D. Hodgkin and Antony Basten

B cell/T cell interaction: an overview of activation

When B cells bind a specific antigen, antibodies on the B cell's membrane are cross-linked. This cross linking initiates internal signaling required for B cell activation. Furthermore, T cell reactivity to the same specific antigen presented by an antigen presenting cell, initiates internal signaling required for T cell activation. Contact and signaling between B and T cells can then result in B cell proliferation. In contrast, the lack of contact or proper signaling of the B cell by a T cell activated by the same antigen as the B cell leads to B cell unresponsiveness or elimination.

The first interaction between B and T cells following immunization occurs in the cen-tral "white pulp" region of the spleen that is also rich in T cells. Some activated B cells then begin to rapidly divide and produce immunoglobulin G (IgG), while others migrate to germinal centers of the spleen to proliferate, to develop further or to differentiate into memory cells.

B cell anergy

Studies in transgenic mice indicate that anergic or unresponsive B cells remain capable of proliferation and production of antibodies if later properly signaled by T cells. Anergic B cells, which have become inactivated but remain alive, are still capable of presenting antigen to T cells. Anergic B cells only express greatly reduced levels of co-stimulatory signals needed for T cell activation during antigen presentation by B cells.

Anergy: two signal theory of B cell activation

Early theories of B cell activation proposed that two signals were required and that lacking one, cells would become "paralyzed." Self-reactive cells would be deleted because of the low probability of two such faulty signals being generated simultaneously. It is now known that mature B cells that have received their first signal rapidly die unless they receive their second signal. The strength of the signal also affects time to death, with strong signals inducing rapid apoptosis in B cells.