Antigen Bridging in the Interaction of T Helper Cells and B Cells

A helper cell population with phenotypic characteristics of both B and T cells is described. This helper population, called BH, is present in normal unprimed C57BL/6 mice and preferentially helps the expression of NPb idiotype-bearing plaque-forming B cells in the absence of T helper cells. Its surface phenotype is Lyt-1.2+, Ig+, Lyb-3+, Thy-1.2-, Lyt-2.2-. The helper activity of the BH population is IgH restricted and BH cells selectively bind NPb idiotypic determinants. Collectively the data demonstrate that this unique subpopulation can regulate the response of antibody-secreting B cells through specific recognition of idiotypic determinants.

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Dual regulation of IRF4 function in T and B cells is required for the coordination of T–B cell interactions and the prevention of autoimmunity

Journal of Experimental Medicine ◽

10.1084/jem.20111195 ◽

2012 ◽

Vol 209 (3) ◽

pp. 581-596 ◽

Cited By ~ 50

Author(s):

Partha S. Biswas ◽

Sanjay Gupta ◽

Roslynn A. Stirzaker ◽

Varsha Kumar ◽

Rolf Jessberger ◽

...

Keyword(s):

Cell Differentiation ◽

B Cells ◽

B Cell ◽

Lupus Erythematosus ◽

T Helper Cells ◽

Regulatory Protein ◽

Cell Interactions ◽

T Helper ◽

T And B Cells ◽

Helper Cells

Effective humoral responses to protein antigens require the precise execution of carefully timed differentiation programs in both T and B cell compartments. Disturbances in this process underlie the pathogenesis of many autoimmune disorders, including systemic lupus erythematosus (SLE). Interferon regulatory factor 4 (IRF4) is induced upon the activation of T and B cells and serves critical functions. In CD4+ T helper cells, IRF4 plays an essential role in the regulation of IL-21 production, whereas in B cells it controls class switch recombination and plasma cell differentiation. IRF4 function in T helper cells can be modulated by its interaction with regulatory protein DEF6, a molecule that shares a high degree of homology with only one other protein, SWAP-70. Here, we demonstrate that on a C57BL/6 background the absence of both DEF6 and SWAP-70 leads to the development of a lupus-like disease in female mice, marked by simultaneous deregulation of CD4+ T cell IL-21 production and increased IL-21 B cell responsiveness. We furthermore show that DEF6 and SWAP-70 are differentially used at distinct stages of B cell differentiation to selectively control the ability of IRF4 to regulate IL-21 responsiveness in a stage-specific manner. Collectively, these data provide novel insights into the mechanisms that normally couple and coordinately regulate T and B cell responses to ensure tight control of productive T–B cell interactions.

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Targeting the CD40-Costimulation Pathway by CFZ533 Prevents the Cross–Talk Between Follicular T Helper Cells and B Cells

Transplantation Journal ◽

10.1097/01.tp.0000543117.99051.48 ◽

2018 ◽

Vol 102 ◽

pp. S366 ◽

Cited By ~ 1

Author(s):

Rens Kraaijeveld ◽

Carla C Baan ◽

Martijn W.F. van den Hoogen

Keyword(s):

B Cells ◽

Cross Talk ◽

T Helper Cells ◽

T Helper ◽

Helper Cells ◽

The Cross ◽

Follicular T Helper Cells

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Mechanism of Follicular Helper T Cell Differentiation Regulated by Transcription Factors

Journal of Immunology Research ◽

10.1155/2020/1826587 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Long-Shan Ji ◽

Xue-Hua Sun ◽

Xin Zhang ◽

Zhen-Hua Zhou ◽

Zhuo Yu ◽

...

Keyword(s):

Transcription Factors ◽

Cell Differentiation ◽

B Cells ◽

T Helper Cells ◽

Molecular Mechanisms ◽

Transcriptional Level ◽

T Helper ◽

Tfh Cells ◽

Helper Cells ◽

Follicular Helper

Helping B cells and antibody responses is a major function of CD4+T helper cells. Follicular helper T (Tfh) cells are identified as a subset of CD4+T helper cells, which is specialized in helping B cells in the germinal center reaction. Tfh cells express high levels of CXCR5, PD-1, IL-21, and other characteristic markers. Accumulating evidence has demonstrated that the dysregulation of Tfh cells is involved in infectious, inflammatory, and autoimmune diseases, including lymphocytic choriomeningitis virus (LCMV) infection, inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), IgG4-related disease (IgG4-RD), Sjögren syndrome (SS), and type 1 diabetes (T1D). Activation of subset-specific transcription factors is the essential step for Tfh cell differentiation. The differentiation of Tfh cells is regulated by a complicated network of transcription factors, including positive factors (Bcl6, ATF-3, Batf, IRF4, c-Maf, and so on) and negative factors (Blimp-1, STAT5, IRF8, Bach2, and so on). The current knowledge underlying the molecular mechanisms of Tfh cell differentiation at the transcriptional level is summarized in this paper, which will provide many perspectives to explore the pathogenesis and treatment of the relevant immune diseases.

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Human Adipose Tissue-Derived Mesenchymal Stem Cells Abrogate Plasmablast Formation and Induce Regulatory B Cells Independently of T Helper Cells

Stem Cells ◽

10.1002/stem.1881 ◽

2015 ◽

Vol 33 (3) ◽

pp. 880-891 ◽

Cited By ~ 91

Author(s):

M. Franquesa ◽

F. K. Mensah ◽

R. Huizinga ◽

T. Strini ◽

L. Boon ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

B Cells ◽

T Helper Cells ◽

Human Adipose Tissue ◽

Regulatory B Cells ◽

T Helper ◽

Helper Cells

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T helper cells grown with hapten-modified cultured Langerhans' cells produce interleukin 4 and stimulate IgE production by B cells

European Journal of Immunology ◽

10.1002/eji.1830190205 ◽

1989 ◽

Vol 19 (2) ◽

pp. 245-252 ◽

Cited By ~ 63

Author(s):

Conrad Hauser ◽

Clifford M. Snapper ◽

Junichi Ohara ◽

William E. Paul ◽

Stephen I. Katz

Keyword(s):

B Cells ◽

T Helper Cells ◽

Langerhans Cells ◽

Interleukin 4 ◽

T Helper ◽

Helper Cells

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Molecular mechanisms for B lymphocyte selection: induction and regulation of antigen-receptor-mediated apoptosis of mature B cells in normal mice and their defect in autoimmunity-prone mice

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.1994.0109 ◽

1994 ◽

Vol 345 (1313) ◽

pp. 297-301 ◽

Cited By ~ 11

Keyword(s):

Immune System ◽

B Cells ◽

B Cell ◽

T Helper Cells ◽

Molecular Mechanisms ◽

B Lymphocyte ◽

Antigen Receptor ◽

Normal Function ◽

T Helper ◽

Helper Cells

Apoptosis (programmed cell death) has been suggested to be involved in clonal elimination of selfreactive lymphocytes for the normal function of the immune system. By crosslinking the antigen receptor (surface immunoglobulin; slg) on the peritoneal B cells of normal mice, we found that strong crosslinking of slg induces apoptosis of mature B cells, suggesting that interaction with membranebound self-antigens may eliminate self-reactive mature B cells by apoptosis. Antigen-receptor-mediated B cell apoptosis is blocked when a signal is transduced via the CD40 molecule on the B cell surface. Because the ligand of CD40 (CD40L) is expressed on activated T helper cells, B cells may escape from apoptosis and are activated when the immune system interacts with foreign antigens, which are normally able to activate T helper cells. Moreover, slg crosslinking fails to induce apoptosis of both bcl-2-transgenic mice and autoimmune-disease-prone New Zealand mice. In these mice, the defect in slg-mediated apoptosis of mature B cells may allow generation of self-reactive B cells, resulting in pathogenic consequences.

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