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Differentiation and Ontogeny of IgM Memory Cells during Bacterial Infection

Award Number: R01AI114545
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: 03/01/2016
PERIOD OF PERFORMANCE END DATE: 02/28/2022

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Differentiation and Ontogeny of IgM Memory Cells during Bacterial Infection - DESCRIPTION (provided by applicant): The long-term goal of our research is to understand the cellular and molecular basis for B cell memory, an essential component of immunity to most pathogens. We have identified a population of IgM-positive memory cells during bacterial infection that, following antigen challenge, give rise to a robust IgG response. The IgM memory cells constitute a novel and important subset of long-lived memory B cells that may provide recall immunity to variant pathogens not recognized by classical high-affinity class-switched memory B cells. We will use our experimental mouse model of human ehrlichiosis to investigate important questions regarding the development and differentiation of IgM memory cells. Our new preliminary data indicate that, following secondary infection, IgM memory cells 1) are responsible for earlier production of IgM, via the generation of long-term IgM-producing cells; 2) undergo further differentiation and diversification within germinal centers; 3) are a source of new class-switched memory cells; and 4) are maintained, as stem cells, by a process of self- renewal. We will address these preliminary findings in greater depth in Aim 1, by first comparing the differentiation and diversification of IgM and switched memory cells following secondary challenge infection, and by evaluating their capacity for protection. We will also formally test th novel hypothesis that the IgM memory cells have the capacity to self-renew and reconstitute a complete spectrum of memory B cells. In Aim 2, we address how the IgM memory cells develop by identifying the B cell subsets which give rise to the memory cells, by testing whether these cells require germinal centers to complete their development, and by investigating how a type of CD4 T cell known as a follicular T cell contributes to IgM memory cell ontogeny. Thus, the proposed research will provide fundamental knowledge of immunological memory, but will also contribute to the design of vaccines and therapies that can elicit durable humoral memory.


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: 2023 ( Subtotal = -$2,987 )
2023	2020	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Allergy and Infectious Diseases Research	000	5	11/7/2022	NON-COMPETING CONTINUATION	-$2,987
														Subtotal = -$2,987

Issue Date FY: 2020 ( Subtotal = $405,000 )
2020	2020	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Allergy and Infectious Diseases Research	000	5	2/13/2020	NON-COMPETING CONTINUATION	$405,000
														Subtotal = $405,000

Issue Date FY: 2019 ( Subtotal = $405,000 )
2019	2019	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Allergy and Infectious Diseases Research	000	4	2/5/2019	NON-COMPETING CONTINUATION	$405,000
														Subtotal = $405,000

Issue Date FY: 2018 ( Subtotal = $405,000 )
2018	2018	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Allergy and Infectious Diseases Research	000	3	2/15/2018	NON-COMPETING CONTINUATION	$405,000
														Subtotal = $405,000

Issue Date FY: 2017 ( Subtotal = $405,000 )
2017	2017	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Allergy and Infectious Diseases Research	000	2	2/14/2017	NON-COMPETING CONTINUATION	$405,000
														Subtotal = $405,000

Issue Date FY: 2016 ( Subtotal = $404,167 )
2016	2016	UNIVERSITY HOSPITAL OF UPSTATE MEDICAL CENTER	750 EAST ADAMS STREET	SYRACUSE	NY	13210	ONONDAGA	USA	Allergy and Infectious Diseases Research	000	1	2/25/2016	NEW	$404,167
														Subtotal = $404,167

Grand Total All Awards = $2,021,180

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Differentiation and Ontogeny of IgM Memory Cells during Bacterial Infection

Award Number: R01AI114545

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: 03/01/2016

PERIOD OF PERFORMANCE END DATE: 02/28/2022

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