The induction of resting B cell differentiation does not require T cell contact

Julius, Michael; Haughn, Lori

doi:10.1002/eji.1830220922

Cited by 5 publications

(6 citation statements)

References 30 publications

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“…Spleen cell suspensions were T-cell depleted by treatment with an anti-T-cell mixture together with a 1:40 dilution of baby rabbit complement (Cedarlane Laboratories) as modified from described procedures (10). Flow cytometric analysis showed that <1% of the cells remaining after this treatment were Thy 1+.…”

Section: Methodsmentioning

confidence: 99%

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Ligation of major histocompatibility complex class II molecules mediates apoptotic cell death in resting B lymphocytes.

Newell

VanderWall

Beard

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

110

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Class 11 major histocompatibility complexencoded molecules expressed on the surface of primed B lymphocytes function as restriction elements for presentation of antigen to T lymphocytes, an interaction that ultimately leads to activation and differentiation of both cell types. The engagement of class 11 on a resting B cell, on the other hand, inhibits subsequent B-cell growth and activation. Our studies show that treatment of resting B lymphocytes with anti-class H antibodies, or with other agents (dibutyryl cAMP or isoproterenol) that increase intracellular levels of cAMP, results in the apoptotic death of most or all of the resting B cells. Conversely, treating cells with immobilized anti-immunoglobulin and interleukin 4, conditions known to prime cells, protects them from class 11-mediated death and specifically from increases in nucleosomal fragments characteristic ofapoptotic death. Freshly ex vivo activated B cells likewise are refractory to class 11-mediated apoptosis. Treating B cells with anti-class II reagents causes an elevatidik of cAMP in resting, but not in activated, B cells. These results suggest that apoptotic death is a mechanism of prevention of nonspecific B-cell activation in the event that T-cell receptor and/or CD4 ligation of major histocompatibility complex class 11 occurs in the absence of antigen.One of the paradigms of modem immunology is that major histocompatibility complex-encoded class II molecules bind and present antigenic peptides to helper T cells during an immune response. More recently, there has been a growing acceptance that class II molecules serve at least one additional function-namely, they are signal transducing receptors on the B cells on which they are expressed. Early studies that demonstrated this signaling function in resting B cells involved crosslinking of class II with monoclonal antibodies (mAbs). The ligation of class II on these cells inhibits subsequent mitogenic signals (1) and results in elevated levels of intracellular cyclic adenosine monophosphate (cAMP). In addition, the increases in cAMP result in translocation of protein kinase C from the cytosol to the nucleus (2) but do not cause increases in intracellular calcium or inositol phospholipid turnover (2). Furthermore, increases in cAMP and omithine decarboxylase activity have been observed in resting B cells after direct contact with fixed T-helper cells (3).Recently, many investigators have established the importance of apoptosis, or programmed cell death, as an effective mechanism for the deletion of unwanted cells, specifically lymphocytes, throughout the immune system (4). This form of cell death is characterized by the generation of nucleosome-sized DNA fragments as a result of activation of endogenous endonuclease(s), which cleaves DNA between nucleosomes (4). We propose that in resting B cells, crosslinking of class II molecules results in programmed cell death in these cells and that this mechanism functions to prevent premature class II-mediated activation of B cells that have not b...

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Section: Methodsmentioning

confidence: 99%

“…T-cell-depleted splenocytes were separated by discontinuous Percoll (Pharmacia) gradients (10). B cells layering at the 1.079/1.085 g/ml (1.079 < p < 1.085) and balanced salt solution (BSS)/1.066 g/ml (p < 1.066) interfaces are designated as resting and activated, respectively.…”

Section: Methodsmentioning

confidence: 99%

Ligation of major histocompatibility complex class II molecules mediates apoptotic cell death in resting B lymphocytes.

Newell

VanderWall

Beard

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

110

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“…One explanation for the difference might be that for the C57 mice, both the Tand the B-cell helper epitopes in the VD4 peptide are on the same peptide, whereas for the C3H mice, which are unable to recognize a T-cell helper epitope in the VD4 peptide, these epitopes are on separate molecules. By using in vitro systems it has been shown that epitopes on separate peptides can act together to produce T-cell bystander help for the B cells, as opposed to cognate help, which results when T-and B-cell epitopes are on the same molecule (11,13,32). In cognate help, where there is physical contact between the two cell types, the resulting antibodies have been shown to be of higher affinity than those produced by bystander help (32).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, the lower neutralizing response exhibited by the C3H mice in this study could be due to lower-affinity antibodies being produced as a result of the physical separation of the B-and T-cell epitopes. Furthermore, it has been shown with Th1 cell clones that close physical contact is needed for differentiation of B cells due to the weak production of interleukin-5 by Th1 cell clones (13). In contrast, Th2 T-cell clones have been reported to support B-cell differentiation in the absence of contact between T and B cells (13).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, it has been shown with Th1 cell clones that close physical contact is needed for differentiation of B cells due to the weak production of interleukin-5 by Th1 cell clones (13). In contrast, Th2 T-cell clones have been reported to support B-cell differentiation in the absence of contact between T and B cells (13). This has been demonstrated in vitro to be mediated in part by interleukin-5 produced in large enough quantities from the Th2 cell clones (13).…”

Section: Discussionmentioning

confidence: 99%

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Immunization with a Peptide Corresponding to Chlamydial Heat Shock Protein 60 Increases the Humoral Immune Response in C3H Mice to a Peptide Representing Variable Domain 4 of the Major Outer Membrane Protein ofChlamydia trachomatis

Motin

Maza

Peterson

1999

Clin Diagn Lab Immunol

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C3H (H-2k ) mice are susceptible to a vaginal challenge with human strains of Chlamydia trachomatis and thus are a useful strain for testing potentialChlamydia vaccine candidates. However, C3H mice are fairly poor responders in terms of the level of antibody resulting from immunization with potential protective peptides representing variable domains (VDs) of the major outer membrane protein (MOMP). C57BL/6 (H-2b ) mice, on the other hand, are moderately resistant to a vaginal challenge but are good responders to the chlamydial MOMP VDs. Peptides representing universal T-cell helper epitopes were employed to determine whether the antibody response to a peptide representing VD4 of the MOMP, which has been shown to contain neutralizing epitopes, could be enhanced in C3H and C57 mice. Universal T-cell helper peptides from tetanus toxin, the pre-S2 region of hepatitis B virus, and the mouse heat shock protein 60, as well as the corresponding segment of the Chlamydia heat shock protein 60 (hspct), were coadministered with the VD4 peptide. Peptides were coencapsulated in liposomes containing the adjuvant monophosphoryl lipid A and administered by using a combination of mucosal and intramuscular injection. The only T-cell helper peptide that improved the immune response as judged by antibody level, in vitro neutralization assays, and T-cell proliferation was hspct. The response in the C57BL/6 strain was not significantly enhanced with hspct over levels achieved with VD4 alone; however, in C3H mice the levels of serum antibody to C. trachomatisincreased to that seen in C57 mice. However, the molecular specificity and immunoglobulin subclass distribution differed from those of the C57 response, and the neutralizing titers and T-cell proliferation responses were lower. In both strains of mice, titers of vaginal antibody to C. trachomatis were low. In summary, of the T-helper peptides used, only hspct significantly enhanced the immune response of C3H mice to the VD4 peptide, but it had only a modest effect on the immune response of C57 mice.

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Interleukin‐2 down‐modulates memory T helper lymphocyte development during antigenic stimulation in vitro

et al. 1995

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Using an in vitro antigenic stimulation model of murine spleen cells in the presence of the immunosuppressor cyclosporin A (CSA) we have previously reported that not only does this drug not interfere with the differentiation of T lymphocytes into memory cells it appears to favor this differentiation (Motta, I. et al., Eur. J. Immunol. 1991. 21:551). Because CSA blocks interleukin-2 (IL-2) gene expression, we have analyzed the effect of this cytokine on memory T helper cell development. Murine splenic cells were primed for 6 days with sheep red blood cells (SRBC) in protocols in which either IL-2 was not produced or its biological activity was neutralized by anti-IL-2 receptor (R) antibodies. The helper function of the recovered T cells was revealed by their capacity to help virgin B splenocytes produce anti-SRBC antibodies upon challenge in vitro. We found that CD4+ cells primed in the absence of IL-2, provoked either by IL-2 gene transcription blockade by CSA or by treatment with anti-IL-2R antibodies, afford the best helper functions. These cells exhibit a memory-type phenotype characterized by the low expression of the MEL-14 marker and the high expression of the CD44 marker. Evidence is also presented that memory T helper cells originate in part from naive subset displaying the MEL-14hi phenotype. The pattern of expression of the genes encoding different cytokines (IL-2, IL-4, IL-5 and interferon-gamma) following a secondary antigenic stimulation shows that the helper function of the cells primed in the absence of IL-2 correlates with the up-regulation of the IL-2 and the IL-5 genes. From these data, we conclude that IL-2 plays a major role in the control of memory T helper cell induction.

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The induction of resting B cell differentiation does not require T cell contact

Cited by 5 publications

References 30 publications

Ligation of major histocompatibility complex class II molecules mediates apoptotic cell death in resting B lymphocytes.

Ligation of major histocompatibility complex class II molecules mediates apoptotic cell death in resting B lymphocytes.

Immunization with a Peptide Corresponding to Chlamydial Heat Shock Protein 60 Increases the Humoral Immune Response in C3H Mice to a Peptide Representing Variable Domain 4 of the Major Outer Membrane Protein ofChlamydia trachomatis

Interleukin‐2 down‐modulates memory T helper lymphocyte development during antigenic stimulation in vitro

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