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Antigen-Presenting B Cells Program the Efferent Lymph T Helper Cell Response

Alsén, Samuel LU ; Cervin, Jakob ; Deng, Yaxiong LU ; Szeponik, Louis ; Wenzel, Ulf Alexander ; Karlsson, Joakim ; Cucak, Helena LU ; Livingston, Megan ; Bryder, David LU and Lu, Qianjin , et al. (2022) In Frontiers in Immunology 13.
Abstract

B cells interact with T follicular helper (Tfh) cells in germinal centers (GCs) to generate high-affinity antibodies. Much less is known about how cognate T–B-cell interactions influence Th cells that enter circulation and peripheral tissues. Therefore, we generated mice lacking MHC-II expressing B cells and, by thoracic duct cannulation, analyzed Th cells in the efferent lymph at defined intervals post-immunization. Focusing on gut-draining mesenteric lymph nodes (MLNs), we show that antigen-specific α4β7+ gut-homing effector Th cells enter the circulation prior to CXCR5+PD-1+ Tfh-like cells. B cells appear to have no or limited impact on the early generation and egress of... (More)

B cells interact with T follicular helper (Tfh) cells in germinal centers (GCs) to generate high-affinity antibodies. Much less is known about how cognate T–B-cell interactions influence Th cells that enter circulation and peripheral tissues. Therefore, we generated mice lacking MHC-II expressing B cells and, by thoracic duct cannulation, analyzed Th cells in the efferent lymph at defined intervals post-immunization. Focusing on gut-draining mesenteric lymph nodes (MLNs), we show that antigen-specific α4β7+ gut-homing effector Th cells enter the circulation prior to CXCR5+PD-1+ Tfh-like cells. B cells appear to have no or limited impact on the early generation and egress of gut-homing Th cells but are critical for the subsequent appearance of Tfh-like cells that peak in the lymph before GCs have developed. At this stage, antigen-presenting B cells also reduce the proportion of α4β7+ Th cells in the MLN and efferent lymph. Furthermore, cognate B-cell interaction drives a broad transcriptional program in Th cells, including IL-4 that is confined to the Tfh cell lineage. The IL-4-producing Tfh-like cells originate from Bcl6+ precursors in the LNs and have gut-homing capacity. Hence, B cells program the efferent lymph Th cell response within a limited window of time after antigenic challenge.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
B cells, efferent lymph, gut-homing CD4 T cells, small intestinal lamina propria, T cells
in
Frontiers in Immunology
volume
13
article number
813203
publisher
Frontiers Media S. A.
external identifiers
  • pmid:35355990
  • scopus:85127291700
ISSN
1664-3224
DOI
10.3389/fimmu.2022.813203
language
English
LU publication?
yes
id
867fb06a-f925-4452-9171-2ba01e694633
date added to LUP
2022-06-07 12:10:03
date last changed
2025-03-07 11:45:30
@article{867fb06a-f925-4452-9171-2ba01e694633,
  abstract     = {{<p>B cells interact with T follicular helper (Tfh) cells in germinal centers (GCs) to generate high-affinity antibodies. Much less is known about how cognate T–B-cell interactions influence Th cells that enter circulation and peripheral tissues. Therefore, we generated mice lacking MHC-II expressing B cells and, by thoracic duct cannulation, analyzed Th cells in the efferent lymph at defined intervals post-immunization. Focusing on gut-draining mesenteric lymph nodes (MLNs), we show that antigen-specific α<sub>4</sub>β<sub>7</sub><sup>+</sup> gut-homing effector Th cells enter the circulation prior to CXCR5<sup>+</sup>PD-1<sup>+</sup> Tfh-like cells. B cells appear to have no or limited impact on the early generation and egress of gut-homing Th cells but are critical for the subsequent appearance of Tfh-like cells that peak in the lymph before GCs have developed. At this stage, antigen-presenting B cells also reduce the proportion of α<sub>4</sub>β<sub>7</sub><sup>+</sup> Th cells in the MLN and efferent lymph. Furthermore, cognate B-cell interaction drives a broad transcriptional program in Th cells, including IL-4 that is confined to the Tfh cell lineage. The IL-4-producing Tfh-like cells originate from Bcl6<sup>+</sup> precursors in the LNs and have gut-homing capacity. Hence, B cells program the efferent lymph Th cell response within a limited window of time after antigenic challenge.</p>}},
  author       = {{Alsén, Samuel and Cervin, Jakob and Deng, Yaxiong and Szeponik, Louis and Wenzel, Ulf Alexander and Karlsson, Joakim and Cucak, Helena and Livingston, Megan and Bryder, David and Lu, Qianjin and Johansson-Lindbom, Bengt and Yrlid, Ulf}},
  issn         = {{1664-3224}},
  keywords     = {{B cells; efferent lymph; gut-homing CD4 T cells; small intestinal lamina propria; T cells}},
  language     = {{eng}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Immunology}},
  title        = {{Antigen-Presenting B Cells Program the Efferent Lymph T Helper Cell Response}},
  url          = {{http://dx.doi.org/10.3389/fimmu.2022.813203}},
  doi          = {{10.3389/fimmu.2022.813203}},
  volume       = {{13}},
  year         = {{2022}},
}