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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Figure 1

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αCD40 treatment aborts a GC phenotype and promotes extrafollicular local...
αCD40 treatment aborts a GC phenotype and promotes extrafollicular localization of Tg B cells. (a) Total numbers of splenic Tg B cells (anti-NP idiotype+, B220+) were measured on day 7 after immunization. (b) Spleen or LN cells from naive (black line), immune/RIgG (red line), and immune/αCD40 (blue line) were stained with GC markers. Histograms shown represent the relative intensity of the indicated marker on Tg B cells (B220+ Id+). (c) Spleen cells from naive and immune IghCD40 transgenic mice treated with rat IgG or agonistic αhCD40 mAb were stained with GC markers. The percentage of total PNA+ GL7+ GC B cells are indicated in each panel. (d) Frozen sections from intact spleens were costained with B220 (green), CD4, and CD8 (red), and anti–NP idiotype (Id) 17.2.25 (blue) Ab’s, and analyzed by confocal microscopy. Objective: ×20; zoom 1.5. Data are representative of three independent experiments.