The murine lymphocyte receptor for IgE, with regard to both structure and function is the focus of this application. Intact FceR levels increase during B cell activation in the presence of interleukin 4 (IL-4) suggesting a role for the FceR in B cell activation. Anti-FceR both in the soluble and sepharose bound form will be tested for the capacity to either directly activate B lymphocytes or to influence B cell activation by anti- Immunoqlobulin. Parameters to be measured include calcium influx, cell size changes, phosphatidyl inositol levels and Ig production. The FceR spontaneously releases lower molecular fragments via proteolysis at the cell surface and preliminary evidence suggests that these fragments enhance the level of IgE synthesis in the presence of IL-4. This phenomena will be further studied with regard to isotype specificity, role of FceR carbohydrate in the biologic activity and molecular size of the FceR fragment involved. In addition, it will be determined if the fragment interacts with a specific component on the B cell membrane. The site of interaction of IgE with the FceR is important with regard to receptor degradation and the location of this site will be explored in detail, both by using anti-peptide antibodies, mimicking specific areas of the FceR and by using crosslinking reagents that will label the site(s) of close proximity with IgE. Antibodies against the site of the FceR that interacts with IgE will also be tested for their capacity to induce FceR upregulation, analogous to IgE and their effect on IgE synthesis will be determined. The low affinity FceR on macrophages and T cells will be further investigated with regard to physiochemical relationship to the B cell FceR, association with other membrane components and regulation at the cell surface. The overall aim is to gain further insight into the structure and regulation of the low affinity FceR and to determine if FceR/anti-FceR related components are useful in the regulation of IgE synthesis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
7R01AI018697-09
Application #
3128120
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1989-05-01
Project End
1992-11-30
Budget Start
1989-05-01
Budget End
1989-11-30
Support Year
9
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Virginia Commonwealth University
Department
Type
Overall Medical
DUNS #
City
Richmond
State
VA
Country
United States
Zip Code
23298
Martin, Rebecca K; Damle, Sheela R; Valentine, Yolander A et al. (2018) B1 Cell IgE Impedes Mast Cell-Mediated Enhancement of Parasite Expulsion through B2 IgE Blockade. Cell Rep 22:1824-1834
Damle, S R; Martin, R K; Cockburn, C L et al. (2018) ADAM10 and Notch1 on murine dendritic cells control the development of type 2 immunity and IgE production. Allergy 73:125-136
Damle, Sheela R; Martin, Rebecca K; Cross, Janet V et al. (2017) Macrophage migration inhibitory factor deficiency enhances immune response to Nippostrongylus brasiliensis. Mucosal Immunol 10:205-214
Lownik, Joseph C; Luker, Andrea J; Damle, Sheela R et al. (2017) ADAM10-Mediated ICOS Ligand Shedding on B Cells Is Necessary for Proper T Cell ICOS Regulation and T Follicular Helper Responses. J Immunol 199:2305-2315
Cooley, Lauren Folgosa; El Shikh, Mohey Eldin; Li, Wei et al. (2016) Impaired immunological synapse in sperm associated antigen 6 (SPAG6) deficient mice. Sci Rep 6:25840
Cooley, Lauren Folgosa; Martin, Rebecca K; Zellner, Hannah B et al. (2015) Increased B Cell ADAM10 in Allergic Patients and Th2 Prone Mice. PLoS One 10:e0124331
Martin, Rebecca K; Brooks, Keith B; Henningsson, Frida et al. (2014) Antigen transfer from exosomes to dendritic cells as an explanation for the immune enhancement seen by IgE immune complexes. PLoS One 9:e110609
Martin, Rebecca K; Saleem, Sheinei J; Folgosa, Lauren et al. (2014) Mast cell histamine promotes the immunoregulatory activity of myeloid-derived suppressor cells. J Leukoc Biol 96:151-9
Folgosa, Lauren; Zellner, Hannah B; El Shikh, Mohey Eldin et al. (2013) Disturbed follicular architecture in B cell A disintegrin and metalloproteinase (ADAM)10 knockouts is mediated by compensatory increases in ADAM17 and TNF-? shedding. J Immunol 191:5951-8
Schlosburg, Joel E; O'Neal, Scott T; Conrad, Daniel H et al. (2011) CB1 receptors mediate rimonabant-induced pruritic responses in mice: investigation of locus of action. Psychopharmacology (Berl) 216:323-31

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