Peyer's patches and other mucosal lymphoid follicles may play several roles in the generation of a secretory immune response manifest at a particular near or distant site: (1) 'antigen-sampling' accomplished by passage of intact macromolecules through specimized dome epithelial cells; (2) clonal expansion of their antigen-sensitive cells stimulated locally by the passaged antigen; (3) provision of a special milieu for generation of more secondary' IgA precursor cells; (4) release of IgA precursors which rapidly become non-recirculating IgA-immunoblasts and lodge in mucosal and exocrine tissue; and (5) release of long-lived, recirculating IgA precursors that can contribute to 'local' secretory immunity at a distant site upon subsequent exposure to antigen there. One overall objective of this project has been to determine how 'environmental' antigens, maternal antibodies passively acquired perinatally, deliberate infections via a mucosal route or deliberate exposure of mucosae to macromolecular, non-living antigens may influence the population of lymphoid cells in murine mucosal follicles and hence prejudice a subsequent secretory, IgA-antibody response by the mouse. A second major objective is to elucidate the molecular bases for (a) sessile-motile transitions occurring in mucosal follicles to release specific lymphoid cells into the circulation; (b) for the restriction of these cells to certain recirculation pathways and to certain blood-tissue egress sites; and (c) for the selective lodging of IgA cells in mucosal or exocrine tissue. A third general objective of our studies is to identify the B-cell/T-cell interactions relevant to the expression and control of a mucosal IgA response and to define the pertinent in vivo sites where these interactions may occur. A final main onjective is to understand, in general, how mucosal follicles come to accumulate such relatively high frequencies of IgA precursor cells of certain specificities and, in particular, the molecular mechanisms operative during the process of B-cell differentiation leading to a commitment to IgA expression.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI017997-08
Application #
3127615
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1980-09-01
Project End
1988-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
8
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
Schools of Arts and Sciences
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Kerlin, R L; Cebra, J J; Weinstein, P D et al. (1994) Sea star factor blocks development of T-dependent antibody secreting clones by preventing lymphokine secretion. Cell Immunol 156:62-76
Cebra, J J; Bos, N A; Cebra, E R et al. (1994) Development of components of the mucosal immune system in SCID recipient mice. Adv Exp Med Biol 355:255-9
George, A; Rath, S; Shroff, K E et al. (1994) Ligation of CD45 on B cells can facilitate production of secondary Ig isotypes. J Immunol 152:1014-21
Hooper, D C; Rubin, D H; Cebra, J J (1994) Spontaneous proliferation of Peyer's patch cells in vitro. Int Immunol 6:873-80
Schrader, C E; Cebra, J J (1993) Dendritic cell dependent expression of IgA by clones in T/B microcultures. Adv Exp Med Biol 329:59-64
Cuff, C F; Cebra, C K; Rubin, D H et al. (1993) Developmental relationship between cytotoxic alpha/beta T cell receptor-positive intraepithelial lymphocytes and Peyer's patch lymphocytes. Eur J Immunol 23:1333-9
Weinstein, P D; Schweitzer, P A; Cebra-Thomas, J A et al. (1991) Molecular genetic features reflecting the preference for isotype switching to IgA expression by Peyer's patch germinal center B cells. Int Immunol 3:1253-63
Weinstein, P D; Cebra, J J (1991) The preference for switching to IgA expression by Peyer's patch germinal center B cells is likely due to the intrinsic influence of their microenvironment. J Immunol 147:4126-35
Cuff, C F; Cebra, C K; Lavi, E et al. (1991) Protection of neonatal mice from fatal reovirus infection by immune serum and gut derived lymphocytes. Adv Exp Med Biol 310:307-15
George, A; Cebra, J J (1991) Responses of single germinal-center B cells in T-cell-dependent microculture. Proc Natl Acad Sci U S A 88:11-5

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