scholarly journals Isotype specificity of helper T cell clones. Peyer's patch Th cells preferentially collaborate with mature IgA B cells for IgA responses.

1984 ◽  
Vol 159 (3) ◽  
pp. 798-811 ◽  
Author(s):  
H Kiyono ◽  
M D Cooper ◽  
J F Kearney ◽  
L M Mosteller ◽  
S M Michalek ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Cultures ◽  
T Helper Cells ◽  
Plasma Cells ◽  
T Helper ◽  
Helper Cells ◽  
A Cells ◽  
Iga Antibody ◽  
B Cell Precursors

The nature of the IgA B cell precursors that receive preferential help from selected clones of T helper cells from mouse Peyer's patches (PP Th A) were studied. Activation of the PP Th A clones required the presence of antigen, sheep erythrocytes (SRBC), in a culture system supporting development of antibody-secreting plasma cells. Two types of PP Th A cells were used. Both gave vigorous IgA responses; the first also supported low IgM, and the second low IgM and IgG subclass antibody responses. Removal of sIgA+ B cells from either splenic or PP B cell cultures selectively depleted precursors of IgA antibody producers. Cultures of purified sIgA+ B cells, cloned PP Th A cells and SRBC, selectively yielded IgA antibody producers. Finally, PP Th A cells did not support IgA responses in B cell cultures derived from spleens of young mice (days 1-25), and full IgA responses were not seen until the donor mice were 6-7 wk of age. These results suggest that cloned T helper cells can recognize and collaborate with mature, IgA committed B cells.

Peripheral B Cells from Patients with MGUS and Multiple Myeloma (MM) Can Be Stimulated by Paraprotein-Target Specific T-Helper Cells to Produce Paraprotein-Identical Monoclonal Antibodies: Rationale for PARs, a Novel Therapeutic Approach with Ultimate Specificity in MGUS/MM

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1817-1817
Author(s):  
Frank Neumann ◽  
Boris Kubuschok ◽  
Klaus-Dieter Preuss ◽  
Claudia Schormann ◽  
Michael Pfreundschuh
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
T Helper Cells ◽  
Plasma Cells ◽  
T Helper ◽  
Helper Cells ◽  
Hla Dr ◽  
Peripheral B Cells

Abstract Background: Paratarg-7 (P-7) is the antigenic target of paraproteins(Preuss et al. Int J Cancer 2009;125:656-61) from 15% of European and 37% of African-American MGUS/MM patients, stronlgy supporting a role of P-7 in the pathogenesis of MGUS/MM via chronic auto-antigenic stimulation. All patients with P-7 specific paraproteins are carriers of the hyperphosphorylated version of p-7 (pP-7). We recently identified pP-7 specific T-helper cells which were restricted by certain "permissive" HLA-DR haplotypes (Neumann et al., Int J Cancer 2015; 137:1076-1084). These HLA-DR subtypes are overrepresented among patients with P-7 specific paraproteins compared to the corresponding normal population indicating that there are two prerequisites for the development of MGUS/MM with a P-7 specific paraprotein: 1st carriership of pP-7 and 2nd a permissive HLA-DR subtype. We now investigated the functional role of the pP-7 specific T-helper cells and their interaction with peripheral B cells with cognate specificity. Methods: Three patients with MGUS or MM, respectively, with a P-7 specific paraprotein and pP-7 specific T-helper cells were included in this study so far. In addition, the B cells from one healthy pP-7 carrying son of one of the patients were also analyzed. In vitro stimulation of antigen-specific peripheral B cells by pP-7 specific T-helper cells followed a modified protocol previously described by Lanzavecchia et al. (Eur J Immunol. 1983; 13:733-738). To this end, CD19+ B cells and CD3+ T cells were magnetically isolated from the proband's PBMC. T cells were replaced by corresponding T-helper cell clones. Results: In all patients studied, the autologous pP-7 specific T-helper cells stimulated the peripheral B cells to produce P-7 specific antibodies. The P-7 specific B-cell responses were monoclonal and the immunoglobulin type was the same as the paraprotein of the corresponding patient. In contrast, B-cell stimulation with CMV-pp65 specific T-helper cells used as controls always induced an antigen-specific, yet polyclonal response. When the peripheral B cells of a pP-7 carrying patient's son were also stimulated with pP-7 specific T-helper cells, they induced - in contrast to the mother - a polyclonal P-7 specific antibody response in his B cells, even though mother and son shared a "permissive" HLA-DR haplotype (HLA-DRB1*1301). Conclusion: In patients with MGUS/MM monoclonal B cells are found in the peripheral blood that can be induced to produce monoclonal antibodies identical to the serum paraprotein by T-helper cells with specificity for the antigenic target of the paraprotein. This does not only support an indispensable role of these T-helper cells in the pathogenesis of MGUS/MM via chronic antigenic stimulation, it also proves that precursors of the malignant plasma cells can be found in the peripheral blood that might fuel the development of malignant plasma cells. Cytogenetic and molecular genetic analyses are underway to determine if these precursor B-cells share the malignant genotype of their malignant plasma cells. These B cells can now be targeted by PARs (p araprotein a ntigens for r everse targeting) conjugated to toxins, as parts of bispecific constructs (PAR/CD3 or PAR/CD16) and/or PAR/CAR T cells. Use of PARs can be envisaged prophylactically for carriers of modified autoantigens like pP-7 with a permissive HLA-DR haplotype and a monoclonal B-cell response in vitro or in MM patients achieving a VGPR or CR after treatment for the prevention of relapse. Disclosures No relevant conflicts of interest to declare.

scholarly journals 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

2012 ◽  
Vol 209 (3) ◽  
pp. 581-596 ◽  
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.

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

1994 ◽  
Vol 345 (1313) ◽  
pp. 297-301 ◽  
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.

Balanced expression of CXCR5 and CCR7 on follicular T helper cells determines their transient positioning to lymph node follicles and is essential for efficient B-cell help

Blood ◽  
2005 ◽  
Vol 106 (6) ◽  
pp. 1924-1931 ◽  
Author(s):  
Svenja Hardtke ◽  
Lars Ohl ◽  
Reinhold Förster
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
T Helper Cells ◽  
Cell Area ◽  
T Helper ◽  
Helper Cells ◽  
Follicular T Helper Cells ◽  
Cell Follicle

Abstract The production of high-affinity antibodies to T-dependent antigens requires the interaction of B cells and T helper cells expressing receptors specific for the same antigen. Although several mechanisms have been elucidated that regulate B-cell trafficking within lymphoid organs, less is known about molecular cues that guide the small subpopulation of CD4+ follicular T helper cells to B-cell follicles. Using adoptive transfer of transgenic T cells in mice, we demonstrate that antigen-induced activation leads to a finely tuned positioning of T cells either to the T-cell area or the B-cell follicle. We show that expression of CXCR5 is indispensable for T cells to enter B-cell follicles, whereas expression of CCR7 provides a counteracting signal to retain activated T cells in the T-cell area. Although only few T cells transiently migrate from the T-cell area to the B-cell follicle of peripheral lymph nodes following antigenic challenge, this step is essential to provide the help B cells require to produce antibodies efficiently. Thus, we demonstrate that the balanced expression of CCR7 and CXCR5 determines the positioning and proper function of follicular T helper cells.

scholarly journals Priming of T helper cells by antigen-activated B cells. B cell-primed Lyt-1+ helper cells are restricted to cooperate with B cells expressing the IgvH phenotype of the priming B cells.

1981 ◽  
Vol 153 (5) ◽  
pp. 1236-1245 ◽  
Author(s):  
J L'Age-Stehr
Keyword(s):  
Immune Response ◽  
B Cells ◽  
B Cell ◽  
Heavy Chain ◽  
T Helper Cells ◽  
Gene Products ◽  
T Helper ◽  
Linked Gene ◽  
Helper Cells ◽  
Activated B Cells

Activated B cells isolated shortly after primary immunization of BALB/c donor mice with sheep erythrocytes (SRBC), were transferred to normal syngeneic recipients or to low-dose cyclophosphamide-pretreated syngeneic recipients. In pretreated recipients, the transfer of activated B cells, but not of T cells or macrophages, resulted in an augmented production of indirect plaque-forming cells in the primary immune response to SRBC but not to horse erythrocytes. It was shown in double-transfer experiments that T helper cells (Lyt-1+) had been stimulated by the transfer of antigen-activated B cells. Criss-cross double-transfer experiments using the mouse strains CB20 and BAB14 (congenic to BALB/c at the loci coding for the immunoglobulin heavy chain) indicate that those T helper cells are primed after recognition of B cell products that are encoded for by genes linked to the loci coding for the variable region of the immunoglobulin heavy chain (IgVH). The thus-primed Ig-dependent T helper cells (THIg) are adaptively restricted to cooperate with B cells that display IgVH-linked gene products similar to those that originally stimulated the THIg. These findings suggest that in the course of an immune response to T cell-dependent antigens, help for the production of specific IgG can be provided by THIg that have been primed and/or clonally expanded after recognition of IgVH-linked gene products by (e.g., complementary) T cell receptors.

scholarly journals The influence of paediatric HIV infection on circulating B cell subsets and CXCR5 + T helper cells

2015 ◽  
Vol 181 (1) ◽  
pp. 110-117 ◽  
Author(s):  
A. Bamford ◽  
M. Hart ◽  
H. Lyall ◽  
D. Goldblatt ◽  
P. Kelleher ◽  
...  
Keyword(s):  
Hiv Infection ◽  
B Cell ◽  
T Helper Cells ◽  
T Helper ◽  
Paediatric Hiv ◽  
Helper Cells ◽  
B Cell Subsets ◽  
Paediatric Hiv Infection

scholarly journals Activated human CD25+B cells are able to induce cell cycle arrest and apoptosis in CD4+T‐Helper cells

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Theresa Tretter ◽  
Ram Kumar Venigalla ◽  
Volker Eckstein ◽  
Rainer Saffrich ◽  
Lorenz Hanns‐Martin
Keyword(s):  
Cell Cycle ◽  
B Cells ◽  
Cell Cycle Arrest ◽  
T Helper Cells ◽  
T Helper ◽  
Induce Cell Cycle Arrest ◽  
Helper Cells ◽  
Cycle Arrest

scholarly journals Role of accessory cells in cytokine production by T cells in chronic B- cell lymphocytic leukemia

Blood ◽  
1995 ◽  
Vol 86 (3) ◽  
pp. 1115-1123 ◽  
Author(s):  
T Decker ◽  
T Flohr ◽  
P Trautmann ◽  
MJ Aman ◽  
W Holter ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell ◽  
T Helper Cells ◽  
Cytokine Production ◽  
Lymphocytic Leukemia ◽  
T Helper ◽  
Ifn Gamma ◽  
Helper Cells ◽  
Accessory Cells ◽  
Normal Individuals

Abstract We investigated the production of cytokines by highly purified T helper cells from B-cell chronic lymphocytic leukemia (B-CLL) patients stimulated by different activation pathways, and we studied the influence of various accessory cell populations on the pattern of the secretion of cytokines, including interleukin (IL)-2, IL-4, interferon- gamma (IFN-gamma), and IL-10. Neither a qualitative nor a quantitative difference in cytokine production and proliferative capacity was observed in CLL-derived purified T cells compared with normal individuals, when T cells were stimulated by different pathways, including CD3, CD2, and costimulation with CD28. Addition of autologous accessory cells (aAC), however, dramatically influenced the cytokine pattern of normal versus B-CLL-derived T cells. CLL cells as aAC caused a marked increase of IL-2, whereas IFN-gamma was only slightly induced and IL-4 was not influenced. In contrast, in normal individuals addition of aAC, which predominantly consisted of monocytes, resulted in a significant increase of IFN-gamma and a reduction of IL-4 secretion. IL-2 production was inhibited by higher concentrations of aAC. The increased stimulation of IL-2 production by CLL cells was not specific to the leukemic cell population, as purified B cells from normal individuals had the same effect. On the other hand, purified monocytes from CLL patients and controls both induced IFN-gamma production and inhibited IL-4 secretion. After antigen-specific stimulation with tetanus toxoid, cytokine secretion was influenced by the type of aAC in a similar pattern. We conclude that T helper cells derived from patients with B-CLL are intrinsically normal and that the predominance of B cells as accessory cells in CLL significantly alters the immune function of T helper cells in vitro.

Sign in / Sign up

Export Citation Format

Share Document