Three classes of signalling molecules on B‐cell membranes

Corley, Ronald B.; Locascio, N. J.; Ovnic, Mariana; Arnold, Larry W.; Pillai, P S; Scott, David W.; Haughton, Geoffrey

doi:10.1002/jcb.240270102

Cited by 13 publications

(6 citation statements)

References 33 publications

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“…These results confirm and extend the data that were generated from studies of the interaction of ascites-derived CH12 cells with heterogeneous populations of splenic TH cells (9)(10)(11) Fig. 1 (Fig.…”

Section: Discussionsupporting

confidence: 80%

“…Previously published studies (9)(10)(11) have established that cells of the murine B-cell lymphoma CH12 can be induced to differentiate and secrete antibody, either nonspecifically by mitogen or specifically by MHC-restricted TH cells plus the antigen which reacts with the surface IgM of CH12. CH12 arose in a B10.H-2aH-4bp/Wts (2a4b) mouse (12).…”

mentioning

confidence: 99%

“…Thus, class II molecules are always involved in TH-cell-B-cell interactions, and in some cases class II molecules alone, without associated antigen, are recognized by T cells. Alloreactive TH cells can mimic the effect of syngeneic, antigen-specific, MHC-restricted TH cells in inducing B-cell differentiation (7)(8)(9)(10).…”

mentioning

confidence: 99%

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Induced differentiation of a transformed clone of Ly-1+ B cells by clonal T cells and antigen.

Bishop¹,

Haughton²

1986

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

115

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The present study used cocultures of clonally derived B and T cells, together with an antigen reactive with the membrane Ig of the clonal B cells, to address the issue of B-cell differentiation requirements. The B cells were CH12.LX, an in vitro grown subclone of a murine B-cell lymphoma, which bears surface IgM reactive with sheep erythrocytes. The T cells were alloreactive T-helper-cell hybridomas. Very small numbers of T-helper cells could induce differentiation of cloned B cells without the presence of accessory cells, but such induction was dependent upon the presence of the antigen recognized by the B cell. Induced differentiation of the B cells did not depend on metabolic activity of the T cells, and metabolically active T cells could be replaced by fixed cells or by monoclonal antibody reactive with the class II molecule of the B cell to deliver an Ia-specific differentiative signal. T cells, or alloantibody that reacted with the I-E molecule, induced differentiation of the B cells; those that reacted with the I-A molecule did not. These results define the minimal requirements for major histocompatibility complex-restricted, T-cell-mediated induction of Bcell differentiation.Antigen-specific interactions between B and T helper (TH) lymphocytes can lead to differentiation and Ig secretion by the B cell. These interactions involve recognition, by the TH cell, of antigen associated with class II major histocompatibility complex (MHC) molecules on the surface of the B cell (1). The series of steps by which antigen becomes associated with class II molecules and thereby becomes visible to the TH cell is termed antigen presentation. Macrophages and B cells are able to present antigen, as are other cell types that bear class II molecules (2-6). Thus, class II molecules are always involved in TH-cell-B-cell interactions, and in some cases class II molecules alone, without associated antigen, are recognized by T cells. Alloreactive TH cells can mimic the effect of syngeneic, antigen-specific, MHC-restricted TH cells in inducing B-cell differentiation (7-10).Previously published studies (9-11) have established that cells of the murine B-cell lymphoma CH12 can be induced to differentiate and secrete antibody, either nonspecifically by mitogen or specifically by MHC-restricted TH cells plus the antigen which reacts with the surface IgM of CH12. CH12 arose in a B10.H-2aH-4bp/Wts (2a4b) mouse (12). It bears surface IgM reactive with sheep erythrocytes (SRBC; ref. 13). Only 0.1-1.0% of CH12 cells secrete antibody spontaneously, but culture with mitogen or with SRBC plus spleen cells containing TH cells of appropriate specificity and H-2 haplotype increased this proportion 10-to 20-fold. Antigenprimed TH cells were able to induce differentiation of CH12 only if derived from mice that share the I-Ek allele with CH12 but not if derived from mice that match with CH12 (k allele) only in the I-A subregion of H-2. Similar results were obtained with alloreactive T-cell lines (11), although flow cytometric analysis showe...

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Section: Discussionsupporting

confidence: 80%

mentioning

confidence: 99%

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Induced differentiation of a transformed clone of Ly-1+ B cells by clonal T cells and antigen.

Bishop¹,

Haughton²

1986

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

115

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“…CH12 serves as a clonal model system for molecular analysis of the late stages of B-cell differentiation and has been found to reflect normal B-cell differentiation processes with high fidelity (13,14,31,38,47,55). We demonstrate here that MMTV gene expression in differentiating B cells is regulated by mechanisms distinct from those that control levels of immunoglobulin and J-chain transcripts and can be regulated independently of functional GR-GRE interactions.…”

mentioning

confidence: 99%

Lipopolysaccharide and dexamethasone induce mouse mammary tumor proviral gene expression and differentiation in B lymphocytes through distinct regulatory pathways.

King¹,

Corley²

1990

Mol. Cell. Biol.

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Endogenous mouse mammary tumor virus (MMTV) proviral transcripts are up regulated during the normal course of B-lymphocyte differentiation. We report here that the regulatory mechanisms which lead to increased levels of MMTV transcripts in differentiating, lipopolysaccharide (LPS)-stimulated normal B cells and in the inducible B-cell lymphoma line CH12 are at least partially distinct from those controlling increases in immunoglobulin and J-chain gene expression. In studies designed to characterize the stimulatory pathways leading to MMTV expression in CH12 cells, we found that stimulation with either LPS or dexamethasone (Dex), a transcriptional activator of MMTV genes, induced not only MMTV expression but also differentiation to antibody secretion. Only Dex-induced and not LPS-induced MMTV expression and differentiation were inhibited by the glucocorticoid antagonist RU486, demonstrating that Dex and LPS stimulate B cells by distinct molecular pathways. Therefore, in B cells, MMTV expression can be regulated via either the conventional hormone receptor-dependent pathway or a hormone receptor-independent pathway. Furthermore, these results suggest that steroid stimulation of B cells can lead to alterations in the expression of other steroid-responsive genes that can become involved in the process of B-cell differentiation.The stimulation of B lymphocytes results in the replication and differentiation of the responding subset into cells that secrete antibodies at a high rate. An understanding of the signal transduction pathways that are involved in the early stages of antigen-specific and mitogen-induced B-cell activation is emerging (reviewed in references 16 and 33), and the molecular events which regulate the increased steady-state expression of immunoglobulin and immunoglobulin-associated J-chain genes, known to be important to the differentiation process, are being characterized (9,11,37,46). Despite advances in these areas, however, the molecular events that are responsible for the differentiation of B cells into antibody-secreting cells remain ill defined. We have approached this problem by identifying and characterizing non-immunoglobulin gene products that are present in higher abundance in differentiating, antibody-secreting cells than in proliferating, non-antibody-secreting cells. We reasoned that an analysis of the molecular events which regulate the inducible expression of such gene products coupled with an understanding of their function should facilitate our understanding of the B-cell differentiation process.Using subtraction analysis, we recently identified a nonimmunoglobulin gene transcript that is expressed in higher abundance in lipopolysaccharide (LPS)-stimulated murine B cells than in unstimulated cells (54). Restriction mapping and sequence analysis of the gene product expressed in the inducible B-cell lymphoma line CH12 revealed that it was encoded by an endogenous mouse mammary tumor virus (MMTV) proviral locus, Mtv-9 (55). Although the cell surface expression of proteins which cross-re...

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“…Various methods have been shown to result in B-lymphocyte proliferation and differentiation in vitro, some of which bypass the requirement for sIg receptor-ligand interactions (6,10,16,18,19), Ia receptor-Th cell interactions (23), or both (5, 7). Indeed, several recent reports (24)(25)(26) have demonstrated that MHCunrestricted Th cell-derived helper factors are apparently able to stimulate resting B cells.…”

mentioning

confidence: 99%

Two separate functions of class II (Ia) molecules: T-cell stimulation and B-cell excitation.

Corley¹,

Locascio²,

Ovnic³

et al. 1985

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

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We have evaluated the role of major histocompatibility complex-encoded class II (Ia) molecules as transmembrane signaling receptors in the T helper cell-dependent activation of B lymphocytes. For these studies, we utilized the murine B-cell lymphoma CH12, which expresses both I-A and I-E class II molecules. In addition, CH12 cells carry IgM of known antigen specificity and require both specific antigen and Ia-restricted T-cell help for the induction of antibody secretion. In this respect, they resemble normal resting B cells. We have studied the ability of antigen-specific or alloreactive T helper cells reactive with either the I-A or the I-E molecules on CH12 to be activated and their ability to stimulate antibody production by CH12. The results show that, although CH12 cells present antigen to T helper cells that interact with either the I-A or the I-E molecules, CH12 cells are stimulated to secrete antibody only by T helper cells reactive with their I-E molecules. Our data demonstrate that class II molecules are transducers of signals for B-cell excitation in addition to serving a restricting function for helper T-cell stimulation. Moreover, the data demonstrate that these two functions, T-cell stimulation and B-cell excitation, are discrete and need not be expressed by the same Ia molecule.

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Three classes of signalling molecules on B‐cell membranes

Cited by 13 publications

References 33 publications

Induced differentiation of a transformed clone of Ly-1+ B cells by clonal T cells and antigen.

Induced differentiation of a transformed clone of Ly-1+ B cells by clonal T cells and antigen.

Lipopolysaccharide and dexamethasone induce mouse mammary tumor proviral gene expression and differentiation in B lymphocytes through distinct regulatory pathways.

Two separate functions of class II (Ia) molecules: T-cell stimulation and B-cell excitation.

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