Maintaining the B Cell Population Requires Receptor Harmony

Immune system researchers have found that the number of immune B cells is maintained at an optimal level through the harmonious activity of two signaling molecules.

Investigators at the University of Pennsylvania School of Medicine (Philadelphia, PA, USA) focused their attention on two B cell surface receptors: the B cell antigen receptor (BCR) and the BLyS receptor 3 (BR3).

Signals propagated through the B cell antigen receptor (BCR) are vital for the development and survival of B cells in both the bone marrow and the periphery. These signals not only guide maturation and activation but also affect the removal of potentially self-reactive B cells.

The tumor necrosis factor (TNF) super family of cytokines includes both soluble and membrane-bound proteins that regulate immune responses. BLyS (B lymphocyte stimulator), a member of the human TNF family, induces B cell proliferation and immunoglobulin secretion. BLyS expression on human monocytes can be upregulated by interferon-gamma. Soluble BLyS functions as a potent B cell growth factor in co-stimulation assays.

Results published in two papers, one in the October 1, 2008, online edition of the  Proceedings of the [U.S.] National Academy of Sciences (PNAS) and the other in the November 2, 2008, online edition of the journal Nature Immunology, presented a clear picture of the interaction between the two types of receptor. "One receptor sends signals to the cell nucleus that says, ‘yes stay alive, the body needs more B cells,' while the other says ‘wait a minute, be careful which B cells are allowed to live',” said senior author Dr. Michael P. Cancro, professor of pathology and laboratory medicine at the University of Pennsylvania School of Medicine.

"There is a steady state number of B cells that is considered normal for humans, and we found that molecular cross talk between two receptors on the surface of B cells balances the need to have enough B cells to make good immune responses, while at the same time guarding against autoimmunity, ” said Dr. Cancro.

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