The B lymphocyte antigen receptor serves the function of internalizing cognate antigen for processing, presenting and signalling in response to antigenic stimulation. Signal transduction may lead to further differentiation, but may also lead to clonal inactivation or deletion, issues that are of relevance for tolerance and autoimmunity. This receptor is made up of a membrane immunoglobulin heavy chain, a light chain, and certainly in the case of the mu isotype, at least two associated chains which are the respective products of the mb-1 and B29 genes. The mb-1 and B29 proteins play a role in the transport of membrane IgM (but not of IgD and IgG) and their postulated roles in antigen presentation and signal transduction are poorly understood. Whether these proteins play any functional role for other isotypes; such as, delta or gamma is not known. Membrane immunoglobulin transport also presumably depends on non-lymphoid gene products which are believed to be molecular chaperons specific for the assembly of membrane (as opposed to secretory) immunoglobulins. Distinct differences between the mu and gamma isotypes in the assembly, degradation and transport of membrane immunoglobulins have been noted, but the molecular bases for these differences are not fully understood.Differences in the internalization and signalling functions of different isotypes has been the subject of very limited study but may be especially relevant for tolerance and disease. The molecular basis for the assembly, transport, intracellular degradation and antigen presentation and signalling functions of mu-m and gamma m will also be investigated by site-directed mutagenesis and transfection approaches.The relevance of the mb-1 and B29 proteins for antigen presentation and signal transduction will be investigated. The structural basis for the interactions of mu-m and gamma m with the p90 and p82 putative molecular chaperons, as well as with mb-1 and B29 will be identified.
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