CD40 ligand-independent B cell activation revealed by CD40 ligand-deficient T cell clones: evidence for distinct activation requirements for antibody formation and B cell proliferation

In this report we have examined the ability of small resting B cells to act as antigen-presenting cells (APC) to antigen-specific MHC-restricted T cells as assessed by either T cell proliferation or T cell-dependent B cell stimulation. We found that 10 of 14 in vitro antigen-specific MHC-restricted T cell clones and lines and three of four T cell hybridomas could be induced to either proliferate or secrete IL-2 in the presence of lightly irradiated (1,000 rads) purified B cells and the appropriate foreign antigen. All T cell lines and hybridomas were stimulated to proliferate or make IL-2 by macrophage- and dendritic cell-enriched populations and all T cells tested except one hybridoma caused B cell activation when stimulated with B cells as APC. Furthermore, lightly irradiated, highly purified syngeneic B cells were as potent a source of APC for inducing B cell activation as were low density dendritic and macrophage-enriched cells. Lymph node T cells freshly taken from antigen-primed animals were also found to proliferate when cultured with purified B cells and the appropriate antigen. Thus, small resting B cells can function as APC to a variety of T cells. This APC function was easily measured when the cells were irradiated with 1,000 rads, but was greatly diminished or absent when they were irradiated with 3,300 rads. Thus, the failure of some other laboratories to observe this phenomenon may be the result of the relative radiosensitivity of the antigen-presenting function of the B cells. In addition, this radiosensitivity allowed us to easily distinguish B cell antigen presentation from presentation by the dendritic cell and macrophage, as the latter was resistant to 3,300 rads. Finally, one T cell clone that failed to proliferate when B cells were used as APC was able to recruit allogeneic B cells to proliferate in the presence of syngeneic B cells and the appropriate antigen. This result suggests that there are at least two distinct pathways of activation in T cells, one that leads to T cell proliferation and one that leads to the secretion of B cell recruitment factor(s).

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Genetic Restriction of Polyclonal Stimulation of B Cell Proliferation by Antigen-Specific T Cell Clones

Ir Genes ◽

10.1007/978-1-4612-5633-5_69 ◽

1983 ◽

pp. 491-495

Author(s):

Sachio Kanamori ◽

Harley Y. Tse

Keyword(s):

Cell Proliferation ◽

T Cell ◽

B Cell ◽

T Cell Clones ◽

Genetic Restriction ◽

Cell Clones ◽

Stimulation Of

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The role of CD154 in haematopoietic development

Thrombosis and Haemostasis ◽

10.1160/th10-03-0174 ◽

2010 ◽

Vol 104 (10) ◽

pp. 639-701 ◽

Cited By ~ 14

Author(s):

Tom Seijkens ◽

David Engel ◽

Marc Tjwa ◽

Esther Lutgens

Keyword(s):

T Cell ◽

B Cell ◽

Cell Activation ◽

Cd40 Ligand ◽

B Cell Activation ◽

Genetic Studies ◽

Therapeutic Implications ◽

Lymphoid Malignancies ◽

Stem And Progenitor Cells

SummaryCD154 (CD40 ligand, CD40L, gp139) is a co-stimulatory molecule of the tumour necrosis factor (TNF) family. CD154 was originally discovered on T-cells, and was found to be involved in many immune responses including B-cell activation, isotype switching, and germinal centre formation. The expression of CD154 on other haematopoietic and nonhaematopoietic cells suggests that CD154 has other functions as well. Indeed, CD154 is involved in many pathological processes, including inflammatory and autoimmune diseases. Genetic studies in patients and mice taught us that CD154 might affect haematopoietic stem and progenitor cells (HSPCs), T-cell, B-cell, and dendritic cell (DC) progenitors. Moreover, the development of specific T-cell and DC subsets critically depends on CD154. Furthermore, CD154 is involved in lymphoid malignancies. Here we highlight the role of CD154 in the developing lymphoid system, including the biology of HSPC and lineage-committed T-cell, B-cell, NK, and DC progenitors. Further, the clinical and therapeutic implications of CD154 interactions in lymphopoiesis will be discussed.

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Characterization of Human CD4+ T-Cell Clones that Secrete Helper Factor(s) for B-Cell Proliferation and Maturation

Scandinavian Journal of Immunology ◽

10.1111/j.1365-3083.1988.tb01483.x ◽

1988 ◽

Vol 28 (5) ◽

pp. 519-527

Author(s):

T. BERZINS ◽

M. VARGAS-CORTES ◽

B. AXELSSON ◽

M.-L. HAMMARSTROM ◽

S. HAMMARSTROM ◽

...

Keyword(s):

Cell Proliferation ◽

T Cell ◽

B Cell ◽

Cd4 T Cell ◽

T Cell Clones ◽

Cell Clones ◽

Helper Factor

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The same human alloreactive T cell clone can help both B lymphocytes and specific cytotoxic precursors.

Journal of Experimental Medicine ◽

10.1084/jem.159.1.318 ◽

1984 ◽

Vol 159 (1) ◽

pp. 318-323 ◽

Cited By ~ 4

Author(s):

D Ramarli ◽

B Parodi ◽

M Fabbi ◽

G Corte ◽

A Lanzavecchia

Keyword(s):

T Cell ◽

B Cell ◽

Cell Activation ◽

Cell Clone ◽

B Cell Activation ◽

Stimulator Cell ◽

Cytotoxic Response ◽

Cell Clones ◽

T Cell Clone ◽

Alloreactive T Cell

Human alloreactive proliferating T cell clones have been compared for their capacity to provide help for B cell activation and the generation of a specific cytotoxic response. The results demonstrate that, when triggered by the relevant alloantigen, the same T cell clone can induce a strong polyclonal B cell activation and serve as the only source of helper cells for the generation of a specific cytotoxic response by any source of CTL precursors against any stimulator cell present in culture.

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COMPLEMENT-DEPENDENT B-CELL ACTIVATION BY COBRA VENOM FACTOR AND OTHER MITOGENS?

Journal of Experimental Medicine ◽

10.1084/jem.139.2.337 ◽

1974 ◽

Vol 139 (2) ◽

pp. 337-354 ◽

Cited By ~ 64

Author(s):

Peter Dukor ◽

Gebhard Schumann ◽

Roland H. Gisler ◽

Manfred Dierich ◽

Wolfgang König ◽

...

Keyword(s):

T Cells ◽

Lymph Node ◽

T Cell ◽

B Cells ◽

B Cell ◽

B Lymphocytes ◽

Cell Cultures ◽

Antibody Formation ◽

Cell Activation ◽

B Cell Activation

It has been proposed that two distinct signals are required for the triggering of the precursors of antibody-forming bone marrow-derived cells (B cells): (a) the binding of antigen or of a mitogen to the corresponding receptor sites on B-cell membranes and (b) the interaction of activated C3 with the C3 receptor of B lymphocytes. There is growing evidence that B-cell mitogens and T (thymus-derived cell)-independent antigens are capable of activating the alternate pathway of the complement system (bypass). Therefore, the effect of another potent bypass inducer was investigated with regard to B-cell activation and the role of C3. Purified, pyrogen-free cobra venom factor was mitogenic for both T and B lymphocytes (cortisone-resistant mouse thymus cells and lymph node lymphocytes from congenitally athymic mice). Venom factor could substitute for T cells by restoring the potential of antibody formation to sheep red blood cells in mouse B-cell cultures supplemented with macrophages or 2-mercaptoethanol. Venom factor may be capable of conferring activated C3 to the C3 receptor of B lymphocytes: preincubation of lymphoid cells with homologous serum or plasma, 10 mM EDTA, and sepharose-coupled venom factor converted with serum to an enzyme active against C3, inhibited their capacity to subsequently form rosettes with sheep erythrocytes sensitized with amboceptor and C5-deficient mouse complement. In the absence of EDTA, preincubation of freshly prepared B-cell suspensions with C3-sufficient homologous serum also blocked their subsequent interaction with complement-sensitized erythrocytes and at the same time rendered them reactive to an otherwise T-cell-specific mitogen. Moreover, mitogen induced B-cell proliferation in lymph node (but not in spleen) cell cultures, appeared to depend on the availability of exogenous C3: zymosan-absorbed fetal bovine serum (only 8.3% site-forming units remaining) supported T-cell activation by phytohemagglutinin, concanavalin A, and venom factor, but failed to sustain B-cell stimulation by pokeweed mitogen, lipopolysaccharide, and venom factor. T-cell-dependent antibody formation in composite cultures containing T cells or T-cell-substituting B-cell mitogens, B cells, and macrophages, always required the presence of C3-sufficient serum.

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