CD22 is a B lymphocyte-specific cell surface glycoprotein which belongs to the immunoglobulin gene superfamily and is highly homologous to numerous cell surface -adhesion molecules. Two independently expressed isoforms of CD22 have been identified and are structurally identical with the exception of two additional Ig-like extracellular domains which are present in the larger isoform, designated CD22beta, and absent from the smaller isoform, CD22alpha. The larger isoform, CD22beta, has been shown to bind T cells, B cells, monocytes and NK cells, and has been shown to bind to several alpha2,6-linked cell surface sialoglycoproteins. CD22beta appears to be involved in B cell interaction with virtually all leukocyte subsets and may clay an important role in the immune response. Most notably, CD22beta interacts with several isoforms of CD45 on T cells and soluble CD22 (CD22Rg) has been shown to modulate early signal transduction events during T cell activation through its direct interaction with CD45. This proposal aims at - elucidating the functional and physiologic role of CD22 during B cell activation as well as T cell-B cell interaction. The focus of this proposal will to be to determine the effect of CD22Rg binding to CD45 on early B cell activation events including calcium flux, phosphorylation of PLCgammal and inositol phosphate production. Additionally, a soluble CD45 chimera will be generated and used in assays to determine whether its binding to B cell CD22 represents a form of reciprocal communication during T cell-B cell interaction. Furthermore, B cells deficient in CD22 will be isolated and transfected with wild type or cytoplasmic deletion mutants to determine the role of the cytoplasmic domain of CD22 during B cell activation. Finally, because previous work has shown that CD22Rg can inhibit T cell activation in vivo, CD22Rg. will be used in in vitro - and in vivo models -of T cell-B cell cooperation and inflammatory disease to determine whether this molecule may be a useful tool to study lymphocyte function and whether it may provide a therapeutic reagent for modulation of autoimmune disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AI001252-02
Application #
2057462
Study Section
Allergy & Clinical Immunology-1 (AITC)
Project Start
1994-09-01
Project End
1997-08-31
Budget Start
1995-09-01
Budget End
1996-08-31
Support Year
2
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199