Short-circuiting long-lived humoral immunity by the heightened engagement of CD40
Loren D. Erickson, … , Hitoshi Kikutani, Randolph J. Noelle
Loren D. Erickson, … , Hitoshi Kikutani, Randolph J. Noelle
Published March 1, 2002
Citation Information: J Clin Invest. 2002;109(5):613-620. https://doi.org/10.1172/JCI14110.
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Article Immunology

Short-circuiting long-lived humoral immunity by the heightened engagement of CD40

Abstract

Agonistic αCD40 Ab’s have been shown to be potent immune adjuvants for both cell- and humoral-mediated immunity. While enhancing short-lived humoral immunity, the administration of a CD40 agonist during thymus-dependent immune responses ablates germinal center formation, prematurely terminates the humoral immune response, blocks the generation of B cell memory, and prevents the generation of long-lived bone marrow plasma cells. Interestingly, some of these effects of heightened CD40 engagement could be mimicked by enhancing the magnitude of antigen-specific T cell help. Taken together, these studies demonstrate that as the magnitude of CD40 signaling intensifies, the fate of antigen-reactive B cells can be dramatically altered. These are the first studies to describe the multifaceted function of CD40 in determining the fate of antigen-reactive B cells and provide novel insights into how CD40 agonists can short-circuit humoral immunity.

Authors

Loren D. Erickson, Brigit G. Durell, Laura A. Vogel, Brian P. O’Connor, Marilia Cascalho, Teruhito Yasui, Hitoshi Kikutani, Randolph J. Noelle

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Carrier-primed T cells prevent the acquisition of a GC phenotype in the ...
Carrier-primed T cells prevent the acquisition of a GC phenotype in the spleen but not in the LN and differentially control the generation of long-lived Tg ASCs. (a) Total numbers of LN and splenic Tg B cells were quantified 5 days after challenge. (b) Tg cells from naive (shaded area) and immune (open area) recipients were stained for the expression of the indicated GC marker. Histograms shown represent the relative intensity on gated Tg cells isolated from LN and spleen. Data are representative of six experiments. (c) Frozen sections from intact spleen and LN were costained with B220 (green), CD4 and CD8 (red), and anti–NP Id 17.2.25 (blue) Ab’s, followed by confocal image analysis. Objective: ×20; zoom: 1.75. (d) Equivalent numbers of naive and immune Tg B cells isolated from spleen and LN of carrier-primed recipients were transferred into secondary recipients that received neither priming nor antigen. Total numbers of bone marrow NP-specific IgG1a ASCs were quantified by ELISPOT analysis 7 days after transfer. Data shown are representative of three independent experiments.