An early CD4+ T cell-dependent immunoglobulin a response to influenza infection in the absence of key cognate T-B interactions

Mark Y. Sangster, Janice M. Riberdy, Maricela Gonzalez, David J. Topham, Nicole Baumgarth, Peter C. Doherty

Research output: Contribution to journalArticle

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Abstract

Contact-mediated interactions between CD4+ T cells and B cells are considered crucial for T cell-dependent B cell responses. To investigate the ability of activated CD4+ T cells to drive in vivo B cell responses in the absence of key cognate T-B interactions, we constructed radiation bone marrow chimeras in which CD4+ T cells would be activated by wild-type (WT) dendritic cells, but would interact with B cells that lacked expression of either major histocompatibility complex class II (MHC II) or CD40. B cell responses were assessed after influenza virus infection of the respiratory tract, which elicits a vigorous, CD4+ T cell-dependent antibody response in WT mice. The influenza-specific antibody response was strongly reduced in MHC II knockout and CD40 knockout mice. MHC II-deficient and CD40-deficient B cells in the chimera environment also produced little virus-specific immunoglobulin (Ig)M and IgG, but generated a strong virus-specific IgA response with virus-neutralizing activity. The IgA response was entirely influenza specific, in contrast to the IgG2a response, which had a substantial nonvirus-specific component. Our study demonstrates a CD4+ T cell-dependent, antiviral IgA response that is generated in the absence of B cell signaling via MHC II or CD40, and is restricted exclusively to virus-specific B cells.

Original languageEnglish (US)
Pages (from-to)1011-1021
Number of pages11
JournalJournal of Experimental Medicine
Volume198
Issue number7
DOIs
StatePublished - Oct 6 2003

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Human Influenza
Immunoglobulins
B-Lymphocytes
T-Lymphocytes
Infection
Major Histocompatibility Complex
Immunoglobulin A
Viruses
Antibody Formation
Virus Diseases
Orthomyxoviridae
Knockout Mice
Respiratory System
Dendritic Cells
Antiviral Agents
Immunoglobulin M
Immunoglobulin G
Bone Marrow
Radiation

Keywords

  • Antibody formation
  • B lymphocytes
  • Immunoglobulin A
  • Mucosal immunity
  • T lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

An early CD4+ T cell-dependent immunoglobulin a response to influenza infection in the absence of key cognate T-B interactions. / Sangster, Mark Y.; Riberdy, Janice M.; Gonzalez, Maricela; Topham, David J.; Baumgarth, Nicole; Doherty, Peter C.

In: Journal of Experimental Medicine, Vol. 198, No. 7, 06.10.2003, p. 1011-1021.

Research output: Contribution to journalArticle

Sangster, Mark Y. ; Riberdy, Janice M. ; Gonzalez, Maricela ; Topham, David J. ; Baumgarth, Nicole ; Doherty, Peter C. / An early CD4+ T cell-dependent immunoglobulin a response to influenza infection in the absence of key cognate T-B interactions. In: Journal of Experimental Medicine. 2003 ; Vol. 198, No. 7. pp. 1011-1021.
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