In both man and mouse it has been shown that the early repertoire of T and B cells differs considerably from that of the adult with respect to V gene family expression, the specificity of receptors and the functions and phenotypes of both lineages. In this proposal we will continue to analyze the developmental regulation of the B cell repertoire in mice. We propose that the Ly1+ B cell subset is a separate lineage of beta cells derived from the omentum and that these cells are primarily responsible for the establishment of the early beta cell repertoire. We will also determine whether the omentum is involved in the extrathymic generation of subsets of T cells. We will investigate at a molecular and cellular level the specificities and lymphocyte activating properties of antibodies produced by these cells as well as their potential to synthesize interleukins which may be involved in the regulation of growth and differentiation of other lymphoid cells. These studies will focus on the origin of these subpopulations of lymphocytes, their role in the ontogeny of the immune response and maintenance of the Beta and T cell repertoires. These experiments may reveal in the long-term why deregulation of Lyl and CD5+ B cells are involved in certain autoimmune and Beta cell neoplastic diseases in mouse and similar diseases in man.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI014782-16
Application #
2060111
Study Section
Immunobiology Study Section (IMB)
Project Start
1978-09-01
Project End
1995-03-31
Budget Start
1993-08-01
Budget End
1995-03-31
Support Year
16
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Microbiology/Immun/Virology
Type
Schools of Dentistry
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Wang, Yong; Schafer, Cara C; Hough, Kenneth P et al. (2018) Myeloid-Derived Suppressor Cells Impair B Cell Responses in Lung Cancer through IL-7 and STAT5. J Immunol 201:278-295
Dickinson, Gregory S; Levenson, Eric A; Walker, Justin A et al. (2018) IL-7 Enables Antibody Responses to Bacterial Polysaccharides by Promoting B Cell Receptor Diversity. J Immunol 201:1229-1240
Patel, Preeyam S; Kearney, John F (2017) CD36 and Platelet-Activating Factor Receptor Promote House Dust Mite Allergy Development. J Immunol 199:1184-1195
Hammad, Hamida; Vanderkerken, Matthias; Pouliot, Philippe et al. (2017) Transitional B cells commit to marginal zone B cell fate by Taok3-mediated surface expression of ADAM10. Nat Immunol 18:313-320
Azzam, Kathleen M; Madenspacher, Jennifer H; Cain, Derek W et al. (2017) Irgm1 coordinately regulates autoimmunity and host defense at select mucosal surfaces. JCI Insight 2:
Patel, Preeyam; Kearney, John F (2016) Immunological Outcomes of Antibody Binding to Glycans Shared between Microorganisms and Mammals. J Immunol 197:4201-4209
Patel, Preeyam S; King, R Glenn; Kearney, John F (2016) Pulmonary ?-1,3-Glucan-Specific IgA-Secreting B Cells Suppress the Development of Cockroach Allergy. J Immunol 197:3175-3187
New, J Stewart; King, R Glenn; Kearney, John F (2016) Manipulation of the glycan-specific natural antibody repertoire for immunotherapy. Immunol Rev 270:32-50
Kearney, John F; Patel, Preeyam; Stefanov, Emily K et al. (2015) Natural antibody repertoires: development and functional role in inhibiting allergic airway disease. Annu Rev Immunol 33:475-504
Wharton, Rebekah E; Stefanov, Emily K; King, R Glenn et al. (2015) Antibodies generated against Streptococci protect in a mouse model of disseminated aspergillosis. J Immunol 194:4387-96

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