Expression of Foxp3 by T follicular helper cells in end-stage germinal centers

Johanne T Jacobsen; Wei Hu; Tiago B R Castro; Sigrid Solem; Alice Galante; Zeran Lin; Samuel J Allon; Luka Mesin; Angelina M Bilate; Ariën Schiepers; Alex K Shalek; Alexander Y Rudensky; Gabriel D Victora

doi:10.1126/science.abe5146

Expression of Foxp3 by T follicular helper cells in end-stage germinal centers

Science. 2021 Jul 16;373(6552):eabe5146. doi: 10.1126/science.abe5146. Epub 2021 Jul 15.

Authors

Johanne T Jacobsen^#¹, Wei Hu^#^{2

3}, Tiago B R Castro^{4

5}, Sigrid Solem⁴, Alice Galante⁴, Zeran Lin⁴, Samuel J Allon^{6

7

8

9

10}, Luka Mesin⁴, Angelina M Bilate⁵, Ariën Schiepers⁴, Alex K Shalek^{6

7

8

9

10

11

12}, Alexander Y Rudensky^{2

3

13}, Gabriel D Victora¹

Affiliations

¹ Laboratory of Lymphocyte Dynamics, The Rockefeller University, New York, NY, USA. jjacobsen@rockefeller.edu victora@rockefeller.edu.
² Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
³ Ludwig Center for Cancer Immunotherapy, New York, NY, USA.
⁴ Laboratory of Lymphocyte Dynamics, The Rockefeller University, New York, NY, USA.
⁵ Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY, USA.
⁶ Institute for Medical Engineering and Science, MIT, Cambridge, MA, USA.
⁷ Department of Chemistry, MIT, Cambridge, MA, USA.
⁸ Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA.
⁹ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
¹⁰ Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹¹ Program in Immunology Harvard Medical School, Boston, MA, USA.
¹² Harvard Stem Cell Institute, Cambridge, MA, USA.
¹³ Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

^# Contributed equally.

Abstract

Germinal centers (GCs) are the site of immunoglobulin somatic hypermutation and affinity maturation, processes essential to an effective antibody response. The formation of GCs has been studied in detail, but less is known about what leads to their regression and eventual termination, factors that ultimately limit the extent to which antibodies mature within a single reaction. We show that contraction of immunization-induced GCs is immediately preceded by an acute surge in GC-resident Foxp3⁺ T cells, attributed at least partly to up-regulation of the transcription factor Foxp3 by T follicular helper (T_FH) cells. Ectopic expression of Foxp3 in T_FH cells is sufficient to decrease GC size, implicating the natural up-regulation of Foxp3 by T_FH cells as a potential regulator of GC lifetimes.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
B-Lymphocytes / immunology*
CD4-Positive T-Lymphocytes / immunology*
CD4-Positive T-Lymphocytes / physiology
Forkhead Transcription Factors / genetics*
Forkhead Transcription Factors / metabolism
Genes, T-Cell Receptor
Germinal Center / cytology
Germinal Center / immunology*
Immunization
Immunophenotyping
Mice
Mice, Inbred C57BL
Mice, Transgenic
Single-Cell Analysis
T Follicular Helper Cells / immunology
T Follicular Helper Cells / metabolism*
T-Lymphocytes, Regulatory / immunology*
T-Lymphocytes, Regulatory / physiology
Up-Regulation

Substances

Forkhead Transcription Factors
Foxp3 protein, mouse

Abstract

Publication types

MeSH terms

Substances

Grants and funding