Immune Netw.  2014 Oct;14(5):227-236. 10.4110/in.2014.14.5.227.

Regulatory T Cells in B Cell Follicles

Affiliations
  • 1College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Korea.
  • 2College of Pharmacy, Seoul National University, Seoul 151-742, Korea. Yeonseok@snu.ac.kr

Abstract

Understanding germinal center reactions is crucial not only for the design of effective vaccines against infectious agents and malignant cells but also for the development of therapeutic intervention for the treatment of antibody-mediated immune disorders. Recent advances in this field have revealed specialized subsets of T cells necessary for the control of B cell responses in the follicle. These cells include follicular regulatory T cells and Qa-1-restricted cluster of differentiation (CD)8+ regulatory T cells. In this review, we discuss the current knowledge related to the role of regulatory T cells in the B cell follicle.

Keyword

Germinal center; B cell; Follicular helper T cell; Foxp3+ regulatory T cell; Qa-1 restricted CD8+ regulatory T cell; Autoantibody

MeSH Terms

Germinal Center
Immune System Diseases
T-Lymphocytes
T-Lymphocytes, Helper-Inducer
T-Lymphocytes, Regulatory*
Vaccines
Vaccines

Figure

  • Figure 1 B cell responses to T-dependent antigens. (1) Naïve CD4+ T cells are activated by dendritic cells presenting cognate antigens in the T cell zones. They transiently express CXCR5 and migrate to the T-B border. B cells recognize their cognate antigens through surface Ig and migrate to the T-B border. In the T-B border, activated CD4+ T cells interact with B cells in an antigen-specific manner, termed "linked recognition." (2) Activated B cells then migrate either to B cell follicles or to the T cell zone. The latter B cells form extrafollicularly and differentiate into short-lived plasma cells with few somatic mutations. (3) Some of the activated CD4+ T cells can acquire characteristics of the Tfh cell lineage and stably express CXCR5. These Tfh cells migrate to the B cell follicle. (4) The activated B cells in B cell follicles are further stimulated by follicular dendritic cells and Tfh cells for multiple rounds. Follicular dendritic cells provide antigens to B cells, leading to the clonal selection of B cells that express high-affinity Ig on their surface. Tfh cells provide IL-21 and costimulation in order to induce the proliferation of B cells, isotype switching, and somatic mutation. The massive B cell expansion and differentiation lead to the formation of germinal centers in the follicle. (4') Tfr cells and CD8+ Treg cells are thought to suppress this germinal center reaction. (5) The germinal center reaction induces the differentiation of isotype-switched affinity-matured B cells into memory B cells or into long-lived plasma cells.

  • Figure 2 Comparison among Tfh, Tfr, and CD8+ Treg cells. Tfh cells express ICOS, PD-1, CD40L, and CXCR5 on the surface, as well as Bcl-6 and Ascl-2 in the nucleus. Similarly, Tfr cells express PD-1, ICOS, and CXCR5, but not CD40L. Unlike Tfh cells, Tfr cells express glucocorticoid-induced TNF receptor-related protein and CTLA4. They also express Foxp3, Bcl-6, and Blimp-1 in the nucleus. Qa-1-reactive CD8+ Treg cells express ICOSL, CD122, and CXCR5. The transcription factor required for the differentiation of this T cell subset remains to be determined.


Cited by  1 articles

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