In healthy adults the total daily production of IgA exceeds that of other immunoglobulin classes. Molecules of representative secretory and serum IgA differ both in their predominant molecular forms (proportion of IgA1 and IgA2 subclasses as well as polymers and monomers) and sites of production. The objective of the proposed investigation is to determine molecular-cellular mechanisms that regulate synthesis and catabolism of IgA. A team of investigators experienced in hybridoma technology and molecular cloning will study the biochemical and genetic events that occur at the earliest stages of human B cell differentiation with the particular emphasis on the importance of J chain expression. This low molecular weight glycoprotein, previously thought to be involved in polymerization and transport of immunoglobulins into external secretions, is likely to have a more fundamental role in B cell ontogeny. It may be expressed before or independently of immunoglobulin chains. Therefore, we shall determine the tissue distribution and properties of J chain-positive cells in unstimulated cells and transformed cell lines of human fetal lymphocytes. The quantity, molecular form, and subcellular localization of J chain will be determined by radioimmunoassay and immunohistochemical procedures. The participation of J chain in the process of intracellular assembly will be explored in vitro and in vivo taking advantage of already available cell lines that express only J chain. These cells will be fused with monomeric IgA-secreting cell lines. Native J chain (obtained from cell lysates or as a cloned products) will be examined for its ability to polymerize monomeric immunoglobulin in vitro. The synthesis of IgA by plasma cells and their precursors is regulated by T cells and/or their products. Thus, we shall study the regulatory role of T cells isolated from human colostrum, the quintessential product of the secretory IgA system. T cells from other sites will be also evaluated for their potential to regulate IgA synthesis in vitro. In contrast to our knowledge of the synthetic sites and large quantitites of IgA produced, its catabolism remains undefined. Accordingly, we shall examine the fate and tissue distribution of catabolized IgA.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI010854-15
Application #
3124827
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1978-08-01
Project End
1991-07-31
Budget Start
1986-08-01
Budget End
1987-07-31
Support Year
15
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Type
Schools of Dentistry/Oral Hygn
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Renegar, Kathryn B; Menge, Alan; Mestecky, Jiri (2006) Influenza virus infection of the murine uterus: a new model for antiviral immunity in the female reproductive tract. Viral Immunol 19:613-22
Takahashi, T; Iwase, T; Takenouchi, N et al. (1996) The joining (J) chain is present in invertebrates that do not express immunoglobulins. Proc Natl Acad Sci U S A 93:1886-91
Crowley-Nowick, P A; Campbell, E; Schrohenloher, R E et al. (1996) Polyethylene glycol precipitates of serum contain a large proportion of uncomplexed immunoglobulins and C3. Immunol Invest 25:91-101
Crowley-Nowick, P A; Campbell, J E; Mullins, A L et al. (1995) Human IgA1 and IgA2 have distinct spectrotypes but display subclass similarities between individuals. Adv Exp Med Biol 371A:591-3
Crowley-Nowick, P A; Bull, R; van den Wall Bake, A W et al. (1994) Immunological studies of IgA nephropathy in blacks reveal elevations of serum IgA2 as well as IgA1. Nephrol Dial Transplant 9:1324-9
Endo, T; Mestecky, J; Kulhavy, R et al. (1994) Carbohydrate heterogeneity of human myeloma proteins of the IgA1 and IgA2 subclasses. Mol Immunol 31:1415-22
Iwase, T; Saito, I; Takahashi, T et al. (1993) Early expression of human J chain and mu chain gene in the fetal liver. Cell Struct Funct 18:297-302
Menge, A C; Mestecky, J (1993) Surface expression of secretory component and HLA class II DR antigen on glandular epithelial cells from human endometrium and two endometrial adenocarcinoma cell lines. J Clin Immunol 13:259-64
Tomana, M; Zikan, J; Moldoveanu, Z et al. (1993) Interactions of cell-surface galactosyltransferase with immunoglobulins. Mol Immunol 30:265-75
Mestecky, J (1993) Saliva as a manifestation of the common mucosal immune system. Ann N Y Acad Sci 694:184-94

Showing the most recent 10 out of 44 publications