The immunoregulatory function of the B lymphocyte receptor for IgE (FcXIR) will be studied. Preliminary studies have indicated that the isolated B lymphocyte FcXIR will suppress the in vitro development of IgE producing plaque forming cells, indicating the potential immunoregulatory role of this molecule. In addition, physico-chemical studies have demonstrated that the B cell FcXIR can be, by limited proteolysis, be converted into carbohydrate containing fragments that are quite similar in size to T cell produced IgE-binding factors. Attempts will be made to produce an FcXIR+ cell line in the murine system via the fusion of B cells from Nippostrongylus brasiliensis (Nb) infected mice with enzyme deficient B cell lines. These FcXIR+ B cell lines and/or B cells isolated from Nb infected mice will serve as a source for the isolation of FcXIR preparations. These will then be studied for their immunoregulatory properties with regard to suppression or enhancement of the IgE and IgG responses in mice. In addition specific FcXIR fragments will be tested in the same manner and compared with the immunoregulatory IgE-binding components isolated from murine T hybridoma cells. The functional role of the FcXIR, while incorporated in the B cell membrane, will also be studied. Preliminary studies have suggested an interaction between FcXIR and B cell surface immunoglobulin (sIg). The modulatory effect that the interaction of FcXIR with sIg during B cell activation, as induced by sIg crosslinking, will be determined. In addition, membrane depolarization effects of B cell FcXIR crosslinking will be studied both in and of itself and in combination with sIg crosslinking.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI022600-03
Application #
3133889
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1985-07-01
Project End
1988-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
Schools of Public Health
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Conrad, D H (1991) Murine CD23/Fc epsilon RII. Structure and function and comparison with the human counterpart. Monogr Allergy 29:9-27
Conrad, D H (1990) Fc epsilon RII/CD23: the low affinity receptor for IgE. Annu Rev Immunol 8:623-45
Conrad, D H (1989) Low affinity IgE receptors (Fc epsilon RII). Clin Rev Allergy 7:165-92
Rao, M; Conrad, D H (1989) IL-4 production by T depleted cells from Nippostrongylus brasiliensis infected mice. Immunol Invest 18:1055-70
Waldschmidt, T J; Conrad, D H; Lynch, R G (1989) Expression of B cell surface receptors. II. IL-4 can accelerate the developmental expression of the murine B cell IgE Fc receptor. J Immunol 143:2820-7
Keegan, A D; Snapper, C M; Van Dusen, R et al. (1989) Superinduction of the murine B cell Fc epsilon RII by T helper cell clones. Role of IL-4. J Immunol 142:3868-74
Tan, K N; Datlof, B M; Gilmore, J A et al. (1988) The T cell receptor V alpha 3 gene segment is associated with reactivity to p-azobenzenearsonate. Cell 54:247-61
Conrad, D H; Keegan, A D; Kalli, K R et al. (1988) Superinduction of low affinity IgE receptors on murine B lymphocytes by lipopolysaccharide and IL-4. J Immunol 141:1091-7
Keegan, A D; Conrad, D H (1987) The murine lymphocyte receptor for IgE. V. Biosynthesis, transport, and maturation of the B cell Fc epsilon receptor. J Immunol 139:1199-205
Lee, W T; Rao, M; Conrad, D H (1987) The murine lymphocyte receptor for IgE. IV. The mechanism of ligand-specific receptor upregulation on B cells. J Immunol 139:1191-8

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