Established T cell-driven germinal center B cell proliferation is independent of CD28 signaling but is tightly regulated through CTLA-4

Lucy S K Walker; Helen E Wiggett; Fabrina M C Gaspal; Chandra R Raykundalia; Margaret D Goodall; Kai-Michael Toellner; Peter J L Lane

doi:10.4049/jimmunol.170.1.91

Established T cell-driven germinal center B cell proliferation is independent of CD28 signaling but is tightly regulated through CTLA-4

J Immunol. 2003 Jan 1;170(1):91-8. doi: 10.4049/jimmunol.170.1.91.

Authors

Lucy S K Walker¹, Helen E Wiggett, Fabrina M C Gaspal, Chandra R Raykundalia, Margaret D Goodall, Kai-Michael Toellner, Peter J L Lane

Affiliation

¹ Department of Pathology, University of California, San Francisco, CA 94143, USA. walkerl@itsa.ucsf.edu

PMID: 12496387
DOI: 10.4049/jimmunol.170.1.91

Abstract

CD4 T cell activation is positively (CD28) and negatively (CTLA-4) regulated by the costimulatory ligands CD80 and CD86. A central question is how the balance between these two opposing forces is controlled as T cells differentiate. We have previously shown that CD28 signaling is absolutely required to prime naive CD4 T cells to differentiate into effectors that provide help for germinal centers and class-switched Ab responses. In this study, we show that the requirement for CD28 signaling is transient and effector CD4 T cells do not require CD28 signals to sustain their function. The CD28 independence of effector T cells within germinal centers suggested that a key function for CD80/CD86 under these circumstances might be to provide negative regulatory signals via the CD28 homologue CTLA-4. By examining germinal center responses in mice where the ability to signal through T cell CTLA-4 was compromised, we provide data that supports a critical role for CTLA-4 in down-regulating T cell help for germinal center B cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Abatacept
Animals
Antibodies, Blocking / administration & dosage
Antibodies, Monoclonal / administration & dosage
Antigens, CD
Antigens, Differentiation / genetics
Antigens, Differentiation / immunology
Antigens, Differentiation / physiology*
B-Lymphocyte Subsets / cytology*
B-Lymphocyte Subsets / immunology*
B-Lymphocyte Subsets / metabolism
CD28 Antigens / genetics
CD28 Antigens / immunology
CD28 Antigens / physiology*
CD4-Positive T-Lymphocytes / cytology
CD4-Positive T-Lymphocytes / immunology*
CTLA-4 Antigen
Cell Division / genetics
Cell Division / immunology
Down-Regulation / genetics
Down-Regulation / immunology
Germinal Center / cytology
Germinal Center / immunology
Immunoconjugates / genetics
Immunoglobulin G / biosynthesis
Immunosuppressive Agents / administration & dosage
Injections, Intraperitoneal
Lymphocyte Cooperation / genetics
Lymphocyte Count
Mice
Mice, Inbred BALB C
Mice, Transgenic
Signal Transduction / genetics
Signal Transduction / immunology*

Substances

Antibodies, Blocking
Antibodies, Monoclonal
Antigens, CD
Antigens, Differentiation
CD28 Antigens
CTLA-4 Antigen
Ctla4 protein, mouse
Immunoconjugates
Immunoglobulin G
Immunosuppressive Agents
Abatacept