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Updated: Jul 16, 2026

Generation of Human CD40-activated B cells
13:27

Generation of Human CD40-activated B cells

Published on: October 16, 2009

Th2-dependent B cell responses in the absence of CD40-CD40 ligand interactions

N Chirmule1, J Tazelaar, J M Wilson

  • 1Institute for Human Gene Therapy, Department of Molecular Engineering, University of Pennsylvania, Philadelphia 19104, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|December 22, 1999
PubMed

Insights

CD40 ligand deficiency impairs humoral immunity. However, activating CD28 on T cells can restore B cell responses, bypassing the need for CD40 signaling on B cells for effective immunity.

Area of Science:

  • Immunology
  • Molecular Biology

Background:

  • CD40 plays a key role in T cell-dependent humoral immunity via antigen presentation and direct B cell activation.
  • Understanding CD40's specific roles in mucosal immunity is crucial for developing effective vaccines and therapies.

Purpose of the Study:

  • To investigate the specific CD40-dependent pathways essential for humoral immunity in the lung mucosa.
  • To determine if CD40 signaling on B cells is indispensable for T helper 2 cell-mediated humoral responses.

Main Methods:

  • Adenovirus-mediated gene transfer of beta-galactosidase (lacZ) into murine lungs.
  • Utilized CD40 ligand-deficient mice to assess CD40-dependent immune responses.
  • Administered anti-CD28 agonistic antibody to reconstitute T cell activation in CD40L-deficient mice.

Main Results:

  • CD40L-deficient mice showed impaired T and B cell responses to adenovirus vector.
  • Systemic CD28 agonistic antibody administration restored T helper 2 cell activation and induced a functional humoral response.
  • This CD28-dependent response generated germinal centers and produced neutralizing anti-adenovirus IgG1 and IgA antibodies.
  • The restored B cell response required CD4+ T cells and was mediated by IL-4.

Conclusions:

  • CD40 signaling on B cells is not essential for generating CD4+ T helper 2 cell-dependent humoral immunity.
  • CD28-costimulated T cells can drive robust humoral immunity independently of direct CD40-B cell interactions.
  • These findings highlight alternative pathways for inducing mucosal humoral immunity.

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