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The biology of type 2 memory B cells and their role in allergy persistence

Award Number: R01AI195716
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: 08/05/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2031

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The biology of type 2 memory B cells and their role in allergy persistence - Project Summary Stereotypical type 2 and type 1 immune responses are driven by specific T cell cytokines IL-4/IL-13 and IFNg, respectively. These cytokines determine the type of the antibody response by regulating class switch recombination (CSR) to different immunoglobulin isotypes. In mice, IL-4 and IL-13 mainly drive production of IgG1 and IgE, while IFNg mediates induction of IgG2a/c. Our laboratory studies the mechanisms that maintain the memory of IgE responses. We found that bona fide IgE memory B cells (MBCs) are absent in type 2 responses, even though antigen-specific IgE antibodies are produced. We determined that germinal center (GC) derived CD73+CD80+ IgG1 MBCs generate high affinity IgE plasma cells (PCs) on reactivation through the mechanism of sequential switching. More recently, we and others discovered human IgG MBCs expressing CD23/FCER2, IL4R, germline IGHE and other IL-4/IL-13 regulated genes. These cells, which we refer to as type 2 (T2) IgG MBCs, contain high affinity allergen-specific clones and are poised to switch to IgE. Human T2 IgG MBCs are different from CXCR3+T-bet+ IgG MBCs, which are typically induced by IFNg. The hypothesis of this application is that GC-derived T2 IgG MBCs play an essential role in allergy persistence because of their readiness to generate high affinity IgE PCs upon activation. This project aims to: 1) determine the role of T2 IgG MBCs and other MBCs in the production of pathogenic IgE; 2) identify unique properties of T2 MBCs in comparison with MBCs induced in type 1 and tolerant responses; 3) Identify factors involved in T2 MBC phenotype stability, survival, and fate determination after activation. Mechanistic studies in vivo will be performed using mouse models of allergy, and of type 1 and tolerant immune responses. In vivo experiments will assess the ability of purified or depleted populations of MBCs to give rise to PCs producing allergen-specific anaphylactic IgE antibodies. MBCs isolated from mice immunized under different polarizing conditions will be compared for their unique transcriptomic, epigenetic and BCR repertoire patterns. Ex-vivo experiments using human B lymphocytes of peripheral blood and tonsils from allergic and non- allergic individuals and B lymphocytes from type 2 immunized mice, will test factors driving fate outcomes of T2 MBCs after activation. We expect that this project will significantly advance the understanding of the B cell memory mechanisms involved in allergen-specific pathogenic IgE production and contribute to the future development of targeted therapies.


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: 2026 ( Subtotal = $816,016 )
2026	2026	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Allergy and Infectious Diseases Research	000	1	8/5/2026	NEW	$816,016
														Subtotal = $816,016

Grand Total All Awards = $816,016

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The biology of type 2 memory B cells and their role in allergy persistence

Award Number: R01AI195716

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: 08/05/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2031

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