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Development of Intestinal Polyreactive IgA B Cells

Award Number: R01AI144094
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/17/2019
PERIOD OF PERFORMANCE END DATE: 12/31/2023

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Development of Intestinal Polyreactive IgA B Cells - A large fraction of the intestinal commensal microbiota is coated with IgA antibodies in homeostatic conditions, but the strategy and the mechanisms deployed to confront the immense diversity of bacterial antigens have remained elusive. Converging studies indicate that homeostatic IgA responses employ a highly polyreactive repertoire to bind broad but distinct subsets of microbiota. These antibody responses develop in the presence of limited T cell help, with low rate of somatic mutations and little affinity maturation. This new perspective contrasts with the classical paradigm of T cell-dependent, high-affinity antibody responses elicited by mucosal pathobionts, pathogens and vaccines, and provides a simple immunological solution to the challenge of microbiota antigenic complexity. It also raises several fundamental issues, including how polyreactive specificities are generated and selected in the IgA repertoire, and how they coexist or overlap with other immune responses during homeostasis and disease. This project addresses these issues by (i) generating polyreactive IgA knock-in mice using CRISPR/Cas9 technology to (ii) understand the development and differentiation of polyreactive IgA precursor B cells and (iii) to study the function of polyreactive IgA at the clonal level in the context of intestinal and extraintestinal challenges. These studies will clarify a major gap in our understanding of polyreactive B cell repertoires, address a challenge to existing dogmas of antibody specificity and tolerance, and develop new knowledge, concepts and tools for a better understanding of intestinal immunity, inflammatory bowel diseases and oral vaccines.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = -$2,219 )
2024	2023	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Allergy and Infectious Diseases Research	000	5	8/7/2024	NON-COMPETING CONTINUATION	-$2,219
														Subtotal = -$2,219

Issue Date FY: 2023 ( Subtotal = $498,426 )
2023	2023	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Allergy and Infectious Diseases Research	000	5	12/14/2022	NON-COMPETING CONTINUATION	$498,426
														Subtotal = $498,426

Issue Date FY: 2022 ( Subtotal = $498,426 )
2022	2022	UNIVERSITY OF CHICAGO, THE	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Allergy and Infectious Diseases Research	000	4	12/21/2021	NON-COMPETING CONTINUATION	$498,426
														Subtotal = $498,426

Issue Date FY: 2021 ( Subtotal = $498,426 )
2021	2021	UNIVERSITY OF CHICAGO, THE	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Allergy and Infectious Diseases Research	000	3	12/22/2020	NON-COMPETING CONTINUATION	$498,426
														Subtotal = $498,426

Issue Date FY: 2020 ( Subtotal = $498,426 )
2020	2020	UNIVERSITY OF CHICAGO, THE	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Allergy and Infectious Diseases Research	000	2	12/30/2019	NON-COMPETING CONTINUATION	$498,426
														Subtotal = $498,426

Issue Date FY: 2019 ( Subtotal = $498,426 )
2019	2019	UNIVERSITY OF CHICAGO, THE	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Allergy and Infectious Diseases Research	000	1	1/15/2019	NEW	$498,426
2019	2019	UNIVERSITY OF CHICAGO, THE	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Allergy and Infectious Diseases Research	001	1	7/1/2019	NEW	$0
														Subtotal = $498,426

Grand Total All Awards = $2,489,911

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Development of Intestinal Polyreactive IgA B Cells

Award Number: R01AI144094

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 01/17/2019

PERIOD OF PERFORMANCE END DATE: 12/31/2023

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