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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI033507-04
Application #
2330381
Study Section
Immunobiology Study Section (IMB)
Project Start
1994-05-01
Project End
1998-01-31
Budget Start
1997-02-01
Budget End
1998-01-31
Support Year
4
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Naikawadi, Ram P; Cheng, Ni; Vogel, Stephen M et al. (2012) A critical role for phosphatidylinositol (3,4,5)-trisphosphate-dependent Rac exchanger 1 in endothelial junction disruption and vascular hyperpermeability. Circ Res 111:1517-27
Faraji, Amir H; Wipf, Peter (2009) Nanoparticles in cellular drug delivery. Bioorg Med Chem 17:2950-62
Moran, Stewart T; Cariappa, Annaiah; Liu, Haoyuan et al. (2006) Protein kinase C-associated kinase is not required for the development of peripheral B lymphocyte populations. Mol Immunol 43:1694-9
Cariappa, Annaiah; Shoham, Tsipi; Liu, Haoyuan et al. (2005) The CD9 tetraspanin is not required for the development of peripheral B cells or for humoral immunity. J Immunol 175:2925-30
Pillai, Shiv; Cariappa, Annaiah; Moran, Stewart T (2005) Marginal zone B cells. Annu Rev Immunol 23:161-96
Pillai, Shiv; Cariappa, Annaiah; Moran, Stewart T (2004) Positive selection and lineage commitment during peripheral B-lymphocyte development. Immunol Rev 197:206-18
Cariappa, Annaiah; Chen, Luojing; Haider, Khaleda et al. (2003) A catalytically inactive form of protein kinase C-associated kinase/receptor interacting protein 4, a protein kinase C beta-associated kinase that mediates NF-kappa B activation, interferes with early B cell development. J Immunol 171:1875-80
Moran, Stewart T; Haider, Khaleda; Ow, Yongkai et al. (2003) Protein kinase C-associated kinase can activate NFkappaB in both a kinase-dependent and a kinase-independent manner. J Biol Chem 278:21526-33
Cariappa, Annaiah; Pillai, Shiv (2002) Antigen-dependent B-cell development. Curr Opin Immunol 14:241-9
Kim, Tae Jin; Cariappa, Annaiah; Iacomini, John et al. (2002) Defective proliferative responses in B lymphocytes and thymocytes that lack neurofibromin. Mol Immunol 38:701-8

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