Pathogens and dietary factors are transported across the gut epithelium. This poses a challenge of discriminating innocuous versus harmful antigens by innate and adaptive immune mechanisms. How B cells contribute to these processes is poorly understood. Moreover, recent studies indicate that B cells also undergo BCR diversification in the GALT, indicating that tolerance mechanisms need to be in place to eliminate newly arising autoreactive B cells. In the proposed work, we will use the conditional expression of a neo-self antigen to investigate B cell tolerance to epithelia-associated antigens in the GALT. This mouse model mimics the situation in some ulcerative colitis patients who produce auto-antibodies to antigens on epithelial cells of the colon. Proof-of-concept for the proposed studies is provided by our preliminary findings, showing that antigens expressed on the gut epithelia can efficiently eliminate self-reactive B cells. Here we will determine how and where these negative selection events take place, and how these processes are affected by a breach in the gut epithelial barrier as it relates to infection and inflammatory bowel disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI122344-02
Application #
9188068
Study Section
Transplantation, Tolerance, and Tumor Immunology (TTT)
Program Officer
Rothermel, Annette L
Project Start
2015-12-01
Project End
2020-11-30
Budget Start
2016-12-01
Budget End
2017-11-30
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Sanford Burnham Prebys Medical Discovery Institute
Department
Type
DUNS #
020520466
City
La Jolla
State
CA
Country
United States
Zip Code
92037
McAllister, Ellen J; Apgar, John R; Leung, Charlotte R et al. (2017) New Methods To Analyze B Cell Immune Responses to Thymus-Dependent Antigen Sheep Red Blood Cells. J Immunol 199:2998-3003