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Extrafollicular Memory B Cell Responses During Influenza Infection

Award Number: F31AI200404
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 07/01/2026
PERIOD OF PERFORMANCE END DATE: 06/30/2029

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Extrafollicular Memory B Cell Responses During Influenza Infection - Protective antibody responses to influenza virus infection are generated in germinal center (GC) reactions, which generate antigen-specific, affinity-matured, class-switched plasma cells as well as memory B cells (MBCs). GC-derived MBCs will respond vigorously to re-encounter, mostly through rapid differentiation to plasmablasts in so-called extrafollicular foci, located outside the primary follicle in the interfollicular and medullary cord areas of the respiratory tract draining mediastinal lymph nodes. Both during primary infection and during recall, extrafollicular responses (EFR) produce antibody- secreting plasmablasts rapidly and prior to GC formation. They are increasingly recognized as essential for early control of viral infections. Regulation of EFR is incompletely understood but known to involve TLR signaling of B cells. These innate signals may contribute to the activation of B cell clones with a broad range of affinities for the activating antigen, resulting in a broadly reactive antibody pool, prioritizing breadth of coverage over specificity. Additionally, the EFR also generates MBCs (EF- MBCs). These memory cells are largely unswitched but antigen-experienced and though to contribute mainly to GC responses following a recall infection. However, EF-MBC generation represents an emerging area of research and their contributions to systemic and tissue-specific long-term immunity remain poorly understood, particularly in terms of their antigenic repertoire and capacity to participate in recall responses. This project aims to test our hypothesis that the EFR generates a broadly reactive antibody pool, that is functionally preserved in the EFR derived MBC compartment, providing heterosubtypic immunity both locally in the respiratory tract and systemically. For that Aim 1 will use single-cell CITE-seq with antigen barcoding of B cells isolated from individual influenza virus A//Puerto Rico 8/34 infected mice to determine the breadth and depths of the virus-specific B cell repertoire of both, plasmablasts and MBCs. Aim 2 will test the functional potential of EF-MBCs in recall responses using adoptive cell transfer of time and Ig-allogenic labeled cells and homo and heterologous challenge of recipient mice. Mice will be analyzed by flow cytometry, ELISA, ELISPOT and affinity measurements of the antibody pool to define and contrast the capacity of EF-MBC for reactivation to that of GC- derived MBCs in the context of both homologous and heterologous influenza viral challenge. By characterizing both the repertoire and functional capacity of EF-derived memory following influenza infection, this work will advance our understanding of an underexplored arm of humoral immunity. These findings may inform future vaccine strategies aimed at eliciting broad, heterosubtypic protection against diverse and evolving influenza strains.


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 = $50,114 )
2026	2026	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	001	1	5/27/2026	NEW	$0
2026	2026	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	000	1	5/27/2026	NEW	$50,114
														Subtotal = $50,114

Grand Total All Awards = $50,114

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Extrafollicular Memory B Cell Responses During Influenza Infection

Award Number: F31AI200404

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 07/01/2026

PERIOD OF PERFORMANCE END DATE: 06/30/2029

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