Margaret M. Harnett

Receptor Signalling and Crosstalk in B Lymphocytes

Eucaryotic cells carry an array of cell surface molecules through which they communicate with their environment. Lymphocytes are no exception, and within recent years it has become increasingly clear that the responses of both T and B lymphocytes to their primary stimuh, i.e. specific antigens, can be modulated by secondary ligand-receptor interactions. In other words, the ultimate response of a particular clonal precursor is regulated by the balance of (either positive or negative) signals received by that cell through a variety of non-antigen-specific receptors. This (fairly self-evident) fundamental concept has recently begun to receive considerable attention, partly because of the availability of increasing numbers of monoclonal antibodies to a variety of cell surface proteins on lymphocytes. The concept puts a new complexion on the problem of immunoregulation. There is no doubt that cell-cell interactions (which have engaged the attentions of several generations of cellular immunologists) are of crucial importance in immune induction and regulation. However, it seems improbable that the increasingly multi-layered and complex cellular circuits which have appeared in the literature within recent years can provide a holistic explanation of how the immune system is regulated. There also have to be simpler mechanisms, and is likely that these will not necessarily be unique to lymphocytes, given that nature tends to be conservative. We will describe here our recent attempts to understand the functions of Bcell receptors, in particular those for antigen (sig), those for the Fc region of IgG antibodies (FcR) and those for certain lymphokines, such as B cell-stimulatory

G protein regulation of receptor signalling

Abstract Binding of agonists to cell surface receptors provokes the release of a variety of intracellular second messenger molecules. There is now substantial evidence that the generation of these second messenger is controlled by a growing family of guanine nucleotide-binding (G) proteins, which couple the receptors to the second messenger-generating system. In this review Margaret Harnett and Gerry Klaus discuss the current evidence for G protein regulation of receptor signalling in cells involved in both innate and adaptive immune responses. Ridgeway, London NW7 1AA, UK.

G-Protein Regulation of Polyphosphoinositide Breakdown in B Cells

It is now well-established that antigen receptors on both T and B lymphocytes belong to the large group of widely distributed Ca2+-mobilizing receptors. In other words, crosslinking of these receptors by anti-receptor antibodies, or antigens, activates a polyphosphoinositide-specific phosphodiesterase (PPI-PDE), whose primary substrate is phosphatidyl-inositol 4,5 bisphosphate (PIP2). This is broken down to inositol 1,4,5-trisphosphate (IP3) and 1,2 diacylglycerol. IP3 causes the release of Ca2+ from intracellular stores, and diacylglycerol is an essential co-factor for the Ca2+ and phospholipid dependent protein kinase C (PKC). In B cells, as in many other cell types, both arms of this branched signalling pathway are required to generate an optimal biological response, in this case activation of resting cells into the cell cycle: this has been demonstrated by the synergistic effects of Ca2+ ionophores and PKC-activating phorbol esters in inducing DNA synthesis in both human and murine B cells. Recent reviews on signalling by surface immunoglobulin (sIg) receptors on B cells can be found in refs. 1 and 2.