CD4 T Follicular Helper Cells Prevent Depletion of Follicular B Cells in Response to Cecal Ligation and Puncture.

Matthew D Taylor,Ana Nedeljkovic-Kurepa,Mariana R Brewer,Clifford S Deutschman,Mabel N Abraham,Kalpana S Reddy,Betsy J Barnes,Yihe Yang

doi:10.3389/fimmu.2020.01946

Abstract

Recent studies have demonstrated that induction of a diverse repertoire of memory T cells (“immune education”) affects responses to murine cecal ligation and puncture (CLP), the most widely – used animal model of sepsis. Among the documented effects of immune education on CLP are changes in T cell, macrophage and neutrophil activity, more pronounced organ dysfunction and reduced survival. Little is known, however, about the effects of CLP on B cell responses, and how these responses might be altered by immune education. Importantly, effective B cell responses are modulated by IL21 produced by CD4+/CXCR5+/PD1+ T follicular helper (Tfh) cells. We examined the B cell population in control and immune educated mice 24 h and 60 days after CLP. Education alone increased Tfh cells. Twenty-four hours after CLP, Tfh cells were depleted. However, this reduction was less pronounced in immune educated mice than in controls and the percentage of CD4 T cells expressing a Tfh phenotype increased in the animals. CLP did not alter splenic architecture and decreased numbers of follicular, marginal, and germinal center B cells. CLP induced changes were not, however, noted following CLP in immune educated mice. At 60 days post – CLP, numbers of follicular, germinal center and marginal zone B cells were increased; this increase was more pronounced in immune educated mice. Finally, while CLP reduced the induction of antigen specific B cells in controls, this response was maintained following CLP in immune educated mice. Our data suggest that preexisting Tfh assists in rescuing the B cell response to CLP.

Highlights

In contrast to other aspects of the immune system, study of the B cell response to sepsis has been limited
Huggins, et al have used co-housing of pathogen free mice with “pet store” mice to increase the number of TLR2+ and TLR4+ phagocytes prior to challenge with Listeria monocytogenes [9] while Sjaastad et al, immunized mice with an MHC-II-restricted peptide following cecal ligation and pucture (CLP) to examine T cell-dependent B cell activation following [10]
Previous studies demonstrated that CLP depleted B cells via apoptosis [1, 15]

Summary

Introduction

In contrast to other aspects of the immune system, study of the B cell response to sepsis has been limited. In contrast to patients and to pet store or “mice in the wild,” laboratory mice lack a memory T cell compartment. This deficiency likely reflects limited exposure to antigenic stimulation in the pathogen-free facilities where lab mice are reared and maintained [7, 8]. We have addressed the contribution of preexisting T cell memory in the mice by inducing widespread T cell memory via administration of an anti-CD3ε activating [11] This procedure, termed “immune education,” led to widespread increase in the numbers of CD4 and CD8 memory T cells.

Methods

Results

Conclusion