scholarly journals Nonspecific activation of murine lymphocytes. I. Proliferation and polyclonal activation induced by 2-mercaptoethanol and alpha-thioglycerol.

1977 ◽  
Vol 145 (3) ◽  
pp. 473-489 ◽  
Author(s):  
M G Goodman ◽  
W O Weigle
Keyword(s):  
T Cell ◽  
B Cell ◽  
Tritiated Thymidine ◽  
Calf Serum ◽  
Blast Transformation ◽  
Spleen Cells ◽  
Thiol Compounds ◽  
Polyclonal Activation ◽  
Cell Responses ◽  
Significant Difference

The effect of 2-mercaptoethanol (2-ME) and alpha-thioglycerol (alpha TG) on proliferation and polyclonal activation of lymphocytes was studied in cultures of spleen cells from C3H mice. Inclusion in serum-free or serum-containing medium of the optimal concentration (5 x 10(-5) M) of either 2-ME or alpha TG resulted in highly significant uptake and incorporation of tritiated thymidine ([3H]TdR) into DNA and in morphological blast transformation. These phenomena were dose-dependent, with both lower and higher doses causing less marked effects. The kinetic peak of these responses was found to occur at day 3 of culture. Improved cellular viability could not explain these results, because by day 3 there was no significant difference in viability between cells cultured in the presence or absence of 2-ME. 2-ME evoked a proliferative response in cultures of congenitally athymic (nu/nu) spleen cells that exhibited a similar but lower dose-response profile compared with that of heterozygous (nu/+) littermates. Cultures of bone marrow-derived (B) lymphocytes, generated by treatment of spleen cells with rabbit antithymocyte serum and complement, incorporated [3H]TdR to a degree at least equal to that of normal spleen cell cultures. Thymus-dependent (T) cells did not support significant 2-ME, alpha TG, or Concanavalin A responses in the absence of serum. However, when cultured in 5% fetal calf serum, definite T-cell responses occurred, though always of a lower magnitude than B-cell responses in this system. When the enriched B-cell and T-cell preparations were co-cultured, a synergistic response was noted. Macrophage dependency of the 2-ME and alpha TG effect was shown to be minimal. It is likely that the greater effectiveness of alpha TG relative to 2-ME is due to differences in the chemical structure of these two thiol compounds. The advantages of utilizing 2-ME and alpha TG as probes in the study of lymphocyte activation are evaluated and their possible mechanisms of action are discussed.

scholarly journals B cell helper factors. I. Requirement for both interleukin 2 and another 40,000 mol wt factor.

1981 ◽  
Vol 154 (5) ◽  
pp. 1681-1693 ◽  
Author(s):  
H J Leibson ◽  
P Marrack ◽  
J W Kappler
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Interleukin 2 ◽  
Spleen Cells ◽  
Con A ◽  
Direct Role ◽  
Cell Responses ◽  
Helper Factor ◽  
Antibody Secreting Cells

A helper factor(s) distinct from interleukin 2 (IL-2) was shown to be present in the concanavalin A-stimulated supernatant of normal mouse spleen cells (normal Con A Sn). Spleen cells thoroughly depleted of T cells required both IL-2 and this factor to produce antibody-secreting cells in response to sheep erythrocytes, although in the presence of IL-2 and a few T cells the requirement for the factor was less apparent. The factor had an apparent approximately 40,000 mol wt. The factor was found in normal Con A Sn that had been depleted of IL-2 by absorption with IL-2-dependent T cells and was absent from Con A-stimulated supernatants of the IL-2-producing T cell hybridoma, FS6-14.13. These results indicate that multiple helper factors control the B cell response to antigen and that IL-2, in addition to its T cell growth promoting activity, plays a direct role in B cell responses.

scholarly journals B cell depletion impairs vaccination-induced CD8+ T cell responses in a type I interferon-dependent manner

2021 ◽  
pp. annrheumdis-2021-220435
Author(s):  
Theresa Graalmann ◽  
Katharina Borst ◽  
Himanshu Manchanda ◽  
Lea Vaas ◽  
Matthias Bruhn ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Expansion ◽  
De Novo ◽  
T Cell Responses ◽  
Type I ◽  
Cell Responses ◽  
T Cell Expansion

ObjectivesThe monoclonal anti-CD20 antibody rituximab is frequently applied in the treatment of lymphoma as well as autoimmune diseases and confers efficient depletion of recirculating B cells. Correspondingly, B cell-depleted patients barely mount de novo antibody responses during infections or vaccinations. Therefore, efficient immune responses of B cell-depleted patients largely depend on protective T cell responses.MethodsCD8+ T cell expansion was studied in rituximab-treated rheumatoid arthritis (RA) patients and B cell-deficient mice on vaccination/infection with different vaccines/pathogens.ResultsRituximab-treated RA patients vaccinated with Influvac showed reduced expansion of influenza-specific CD8+ T cells when compared with healthy controls. Moreover, B cell-deficient JHT mice infected with mouse-adapted Influenza or modified vaccinia virus Ankara showed less vigorous expansion of virus-specific CD8+ T cells than wild type mice. Of note, JHT mice do not have an intrinsic impairment of CD8+ T cell expansion, since infection with vaccinia virus induced similar T cell expansion in JHT and wild type mice. Direct type I interferon receptor signalling of B cells was necessary to induce several chemokines in B cells and to support T cell help by enhancing the expression of MHC-I.ConclusionsDepending on the stimulus, B cells can modulate CD8+ T cell responses. Thus, B cell depletion causes a deficiency of de novo antibody responses and affects the efficacy of cellular response including cytotoxic T cells. The choice of the appropriate vaccine to vaccinate B cell-depleted patients has to be re-evaluated in order to efficiently induce protective CD8+ T cell responses.

scholarly journals A MOUSE B-CELL ALLOANTIGEN DETERMINED BY GENE(S) LINKED TO THE MAJOR HISTOCOMPATIBILITY COMPLEX

1973 ◽  
Vol 138 (6) ◽  
pp. 1289-1304 ◽  
Author(s):  
David H. Sachs ◽  
James L. Cone
Keyword(s):  
Major Histocompatibility Complex ◽  
Lymph Node ◽  
T Cell ◽  
B Cells ◽  
Cell Surface ◽  
B Cell ◽  
Surface Antigen ◽  
Major Histocompatibility ◽  
Spleen Cells ◽  
Histocompatibility Complex

Antibodies cytotoxic for only a subpopulation of C57Bl/10 lymph node and spleen cells were detected when rat antiserum against B10.D2 was exhaustively absorbed with B10.A lymphocytes. Antibodies of similar specificity were also detected in B10.A anti-B10.D2 and in B10.A anti-C57Bl/10 alloantisera. Reactions with recombinant strains of mice indicate that the cell-surface antigen(s) responsible for this specificity is determined by gene(s) in or to the left of the Ir-1 region of the major histocompatibility complex. A variety of criteria implicate B cells as the subpopulation of lymphocytes bearing this antigen. In view of these data and the recent report by others of a T-cell alloantigen determined by gene(s) in the major histocompatibility complex, it seems possible that there may be a variety of H-2-linked alloantigens expressed preferentially on subclasses of lymphocytes.

scholarly journals Enhanced T- and B-cell responses to simian immunodeficiency virus (SIV)agm, SIVmac and human immunodeficiency virus type 1 Gag DNA immunization and identification of novel T-cell epitopes in mice via codon optimization

2009 ◽  
Vol 90 (10) ◽  
pp. 2513-2518 ◽  
Author(s):  
Christine S. Siegismund ◽  
Oliver Hohn ◽  
Reinhard Kurth ◽  
Stephen Norley
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
B Cell ◽  
Simian Immunodeficiency Virus ◽  
Codon Optimization ◽  
T Cell Epitopes ◽  
Gm Csf ◽  
Cell Responses ◽  
Immunodeficiency Virus

As a prelude to primate studies, the immunogenicity of wild-type and codon-optimized versions of simian immunodeficiency virus (SIV)agm Gag DNA, with and without co-administered granulocyte–macrophage colony-stimulating factor (GM-CSF) DNA, was directly compared in two strains of mice. Gag-specific T cells in the splenocytes of BALB/c and C57BL/6 mice immunized by gene gun were quantified by ELISpot using panels of overlapping synthetic peptides (15mers) spanning the entire capsid proteins of SIVagm, SIVmac and human immunodeficiency virus type 1. Specific antibodies were measured by ELISA. Codon optimization was shown to significantly increase the immune response to the DNA immunogens, reducing the amount of DNA necessary to induce cellular and antibody responses by one and two orders of magnitude, respectively. Co-administration of murine GM-CSF DNA was necessary for the induction of high level T- and B-cell responses. Finally, it was possible to identify both known and novel T-cell epitopes in the Gag proteins of the three viruses.

scholarly journals CD40 in Clinical Inflammation: From Multiple Sclerosis to Atherosclerosis

1998 ◽  
Vol 6 (3-4) ◽  
pp. 215-222 ◽  
Author(s):  
Jon D. Laman ◽  
Mark De Boer ◽  
Bert A. 'T Hart
Keyword(s):  
Multiple Sclerosis ◽  
Dendritic Cells ◽  
T Cell ◽  
B Cell ◽  
Antibody Production ◽  
Memory Formation ◽  
Isotype Switching ◽  
Cell Responses ◽  
Clinical Conditions ◽  
Antigen Presenting

The interactions of CD40 and CD40L have been known for some time to critically regulate B-cell responses with respect to proliferation, isotype switching, antibody production, and memory formation. More recent findings demonstrated that CD40 can be expressed on several other antigen-presenting cell (APC) types such as macrophages, dendritic cells, and fibroblasts. This expression of CD40 regulates T-cell-APC interaction and is centrally involved in a wide array of inflammatory events. Here, currently available data are reviewed demonstrating that CD40- CD40L interactions are operational in two chronic inflammatory clinical conditions, namely, multiple sclerosis and atherosclerosis. The functional correlates of these interactions are discussed in the light of recent other findings, shedding light on the multiple effects of CD40- CD40L interactions.

AB0144 STRATIFICATION OF PATIENTS WITH PRIMARY SJÖGREN’S SYNDROME BY MEASURING B-CELL HEALTH

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1372-1373
Author(s):  
G. M. Verstappen ◽  
J. C. Tempany ◽  
H. Cheon ◽  
A. Farchione ◽  
S. Downie-Doyle ◽  
...  
Keyword(s):  
Cell Division ◽  
Cell Differentiation ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
B Cell Differentiation ◽  
Research Support ◽  
Differentiation Capacity ◽  
Cell Responses ◽  
Healthy Donors

Background:Primary Sjögren’s syndrome (pSS) is a heterogeneous immune disorder with broad clinical phenotypes that can arise from a large number of genetic, hormonal, and environmental causes. B-cell hyperactivity is considered to be a pathogenic hallmark of pSS. However, whether B-cell hyperactivity in pSS patients is a result of polygenic, B cell-intrinsic factors, extrinsic factors, or both, is unclear. Despite controversies about the efficacy of rituximab, new B-cell targeting therapies are under investigation with promising early results. However, for such therapies to be successful, the etiology of B-cell hyperactivity in pSS needs to be clarified at the individual patient level.Objectives:To measure naïve B-cell function in pSS patients and healthy donors using quantitative immunology.Methods:We have developed standardised, quantitative functional assays of B-cell responses that measure division, death, differentiation and isotype switching, to reveal the innate programming of B cells in response to T-independent and dependent stimuli. This novel pipeline to measure B-cell health was developed to reveal the sum total of polygenic defects and underlying B-cell dysfunction at an individual level. For the current study, 25 pSS patients, fulfilling 2016 ACR-EULAR criteria, and 15 age-and gender-matched healthy donors were recruited. Standardized quantitative assays were used to directly measure B cell division, death and differentiation in response to T cell-independent (anti-Ig + CpG) and T-cell dependent (CD40L + IL-21) stimuli. Naïve B cells (IgD+CD27-) were sorted from peripheral blood mononuclear cells and were labeled with Cell Trace Violet at day 0 to track cell division until day 6. B cell differentiation was measured at day 5.Results:Application of our standardized assays, and accompanying parametric models, allowed us to study B cell-intrinsic defects in pSS patients to a range of stimuli. Strikingly, we demonstrated a hyperresponse of naïve B cells to combined B cell receptor (BCR) and Toll-like receptor (TLR)-9 stimulation in pSS patients. This hyperresponse was revealed by an increased mean division number (MDN) at day 5 in pSS patients compared with healthy donors (p=0.021). A higher MDN in pSS patients was observed at the cohort level and was likely attributed to an increased division burst (division destiny) time. The MDN upon BCR/TLR-9 stimulation correlated with serum IgG levels (rs=0.52; p=0.011). No difference in MDN of naïve B cells after T cell-dependent stimulation was observed between pSS patients and healthy donors. B cell differentiation capacity (e.g., plasmablast formation and isotype switching) after T cell-dependent stimulation was also assessed. At the cohort level, no difference in differentiation capacity between groups was observed, although some pSS patients showed higher plasmablast frequencies than healthy donors.Conclusion:Here, we demonstrate defects in B-cell responses both at the cohort level, as well as individual signatures of defective responses. Personalized profiles of B cell health in pSS patients reveal a group of hyperresponsive patients, specifically to combined BCR/TLR stimulation. These patients may benefit most from B-cell targeted therapies. Future studies will address whether profiles of B cell health might serve additional roles, such as prediction of disease trajectories, and thus accelerate early intervention and access to precision therapies.Disclosure of Interests:Gwenny M. Verstappen: None declared, Jessica Catherine Tempany: None declared, HoChan Cheon: None declared, Anthony Farchione: None declared, Sarah Downie-Doyle: None declared, Maureen Rischmueller Consultant of: Abbvie, Bristol-Meyer-Squibb, Celgene, Glaxo Smith Kline, Hospira, Janssen Cilag, MSD, Novartis, Pfizer, Roche, Sanofi, UCB, Ken R. Duffy: None declared, Frans G.M. Kroese Grant/research support from: Unrestricted grant from Bristol-Myers Squibb, Consultant of: Consultant for Bristol-Myers Squibb, Speakers bureau: Speaker for Bristol-Myers Squibb, Roche and Janssen-Cilag, Hendrika Bootsma Grant/research support from: Unrestricted grants from Bristol-Myers Squibb and Roche, Consultant of: Consultant for Bristol-Myers Squibb, Roche, Novartis, Medimmune, Union Chimique Belge, Speakers bureau: Speaker for Bristol-Myers Squibb and Novartis., Philip D. Hodgkin Grant/research support from: Medimmune, Vanessa L. Bryant Grant/research support from: CSL

scholarly journals High-titer lentiviral vectors stimulate fetal calf serum-specific human CD4 T-cell responses: implications in human gene therapy

Gene Therapy ◽  
2009 ◽  
Vol 16 (6) ◽  
pp. 788-795 ◽  
Author(s):  
L Bao ◽  
H Guo ◽  
X Huang ◽  
S Tammana ◽  
M Wong ◽  
...  
Keyword(s):  
Gene Therapy ◽  
T Cell ◽  
Fetal Calf Serum ◽  
Human Gene ◽  
High Titer ◽  
Calf Serum ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Human Gene Therapy ◽  
Cell Responses

scholarly journals The role of H-2-linked genes in helper T cell function. VII. Expression of I region and immune response genes by B cells in bystander help assays.

1980 ◽  
Vol 152 (5) ◽  
pp. 1274-1288 ◽  
Author(s):  
P Marrack ◽  
J W Kappler
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Function ◽  
High Responder ◽  
Helper T Cells ◽  
Spleen Cells ◽  
Region Gene ◽  
Immunoglobulin Receptor

The mode of action by bystander helper T cells was investigated by priming (responder X nonresponder) (B6A)F1 T cells with poly-L-(Tyr, Glu)-poly-D,L-Ala--poly-L-Lys [(TG)-A--L] and titrating the ability of these cells to stimulate an anti-sheep red blood cell (SRBC) response of parental B cells and macrophages in the presence of (TG)-A--L. Under limiting T cell conditions, and in the presence of (TG)-A--L, (TG)-A--L-responsive T cells were able to drive anti-SRBC responses of high-responder C57BL/10.SgSn (B10) B cells and macrophages (M0), but not of low-responder (B10.A) B cells and M0. Surprisingly, the (TG)-A--L-driven anti-SRBC response of B10.A B cells was not restored by addition of high-responder acessory cells, in the form of (B6A)F1 peritoneal or irradiated T cell-depleted spleen cells, or in the form of B10 nonirradiated T cell-depleted spleen cells. These results suggested that (TG)-A--L-specific Ir genes expressed by B cells controlled the ability of these cells to be induced to respond to SRBC by (TG)-A--L-responding T cells, implying that direct contact between the SRBC-binding B cell precursor and the (TG)-A--L-responsive helper T cells was required. Analogous results were obtained for keyhold limpet hemocyanin (KLH)-driven bystander help using KLH-primed F1 T cells restricted to interact with cells on only one of the parental haplotypes by maturing them in parental bone marrow chimeras. It was hypothesized that bystander help was mediated by nonspecific uptake of antigen [(TG)-A--L or KLH] by SRBC-specific b cells and subsequent display of the antigen on the B cell surface in association with Ir of I-region gene products, in a fashion similar to the M0, where it was then recognized by helper T cells. Such an explanation was supported by the observation that high concentrations of antigen were required to elicit bystander help. This hypothesis raises the possibility of B cell processing of antigen bound to its immunoglobulin receptor and subsequent presentation of antigen to helper T cells.

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