Distinct helper activities control growth or maturation of B lymphocytes

Pettersson, Sven; Pobor, Grgur; Bandeira, António; Coutinho, António

doi:10.1002/eji.1830130314

Cited by 21 publications

(9 citation statements)

References 30 publications

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“…These results are consistent with a two-step model of B cell activation [ll]: upon direct and specific cellular interaction, Th cells render B cells responsive to nonspecific growth and maturation factors [12,201 and, in parallel, Th cells also produce or participate in the production of these unspecific factors.…”

Section: Discussionsupporting

confidence: 88%

“…We have recently isolated a clone of Th cells that induces extensive B cell proliferation, but lacks the ability to produce B cell maturation factor and fails, therefore, to support B cell maturation to secretion of Ig [12]. Although this clone seems to be a rare variant, AL-4 and AL-A3 cells were also assayed for induction of PFC responses to ascertain that they are fully competent "helpers".…”

Section: Induction Of Ig Secretion By Mhc-reactive Th Cellsmentioning

confidence: 98%

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B lymphocyte activation upon exclusive recognition of major histocompatibility antigens by T helper cells

et al. 1984

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This study has investigated whether exclusive recognition of I-A or I-E molecules on the B cell surface by T helper cells is sufficient to activate resting B cells. Lines and clones of long-term-cultured T helper cells with specificity for I-A or I-E antigens have been derived from mixed lymphocyte cultures between spleen cells from major histocompatibility complex (MHC)-congenic mouse strains. These cells were tested for helper activity and proved competent to induce resting B lymphocytes expressing the specific MHC antigens to polyclonal expansion and maturation to Ig secretion. B cell activation was shown to require direct recognition of I-A/E antigens by the helper cells on the responding B lymphocyte surface and it could not be achieved by soluble factors released by "third-party" helper cell activity ongoing in the same cultures. Since B lymphocyte activation occurs in the absence of antigen recognition by the responding B cells, these observations suggest that I-A and I-E molecules expressed on the B cell surface participate in the functional reception of T helper cell-derived induction signals.

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Section: Discussionsupporting

confidence: 88%

Section: Induction Of Ig Secretion By Mhc-reactive Th Cellsmentioning

confidence: 98%

B lymphocyte activation upon exclusive recognition of major histocompatibility antigens by T helper cells

et al. 1984

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“…Likewise, it may well be that changes of precursor frequencies during ontogeny as they have been found in the T15 system again by using the splenic focus assay [54].…”

Section: Limitations Of Analysis and Conclusionmentioning

confidence: 99%

The expression of a set of antibody variable regions in lipopolysaccharide‐reactive B cells at various stages of ontogeny and its control by anti‐idiotypic antibody

1983

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An analysis is presented in which we measure the expression of a subset of antibody variable (V) regions in lipopolysaccharide (LPS)-reactive precursor B cells at various stages of ontogeny. The V regions were characterized by hapten (4-hydroxy-3-nitrophenyl)acetyl (NP)-binding specifity and/or expression of idiotypic determinants whose genetic basis had been explored in previous studies. Only V regions containing the V lambda 1 domain were considered: this allowed an unequivocal determination of idiotopes and reduced heterogeneity in the system essentially to the multiplicity of VH and D genes. It was found that approximately every fourth lambda 1-bearing LPS-reactive splenic B cell produces an NP-binding antibody. Approximately 1 in 40 lambda 1-bearing cells expressed an idiotope (Ac38) which is encoded by V lambda 1 and a set of related VH genes in combination with D and J elements. Of these cells, only a minority produce an NP-binding antibody and a few percent of the latter express a second idiotope (Ac146) which is known to be restricted to a subset of Ac38-positive, NP-binding humoral antibodies. All these frequencies are in good accord with previous analyses of anti-idiotope-induced antibodies in the serum. They can be easily accommodated into a simple model of random selection of VH genes in LPS-reactive B lymphocytes. The frequencies of the V regions under study were essentially the same in LPS-reactive B cells from spleens of adult and newborn animals and in LPS-reactive B cells generated from bone marrow pre-B cells in vitro. In the case of the latter cells the frequencies were independent of the absence or presence of T cells in the culture system. While we could thus detect, in naive mice, neither positive nor negative selection of the cells from the time of their generation in the bone marrow until their arrival in the periphery, negative selection is in principle possible: the presence of microgram amounts of anti-idiotope antibodies during maturation from pre-B to B cells specifically blocks the appearance of idiotope-bearing LPS-reactive cells in vitro. The potential physiological role of the latter effect in the sense of self-stabilization of the expressed antibody repertoire in ongoing immune responses and the possibility that frequency determinations in LPS-reactive B cells may be not representative for the repertoire expressed in the population of mature B cells is discussed.

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“…The analysis of B cell responses stimulated by helper T lymphocytes has revealed three distinct phases: (1) induction of resting B lymphocytes to a state of reactivity to nonspecific factors [8], which requires direct cell-to-cell interactions and participation of IA and IE molecules recognized on the responding B cell membrane by allospecific [9] or major histocompatibility complex (MHC)-restricted helper cells [10]; (2) proliferation of "induced" B cells upon interaction of cell type-specific growth factors (BCGF) with appropriate receptors, which are not expressed by resting cells [11]; and (3) maturation of proliferating B cells, regulated by nonspecific factors (BCMF) competent for stimulating increased rates of synthesis and secretion of immunoglobulins [12,13]. At least one type of BCGF is produced by T lymphocytes, and although definitive evidence is still lacking in this respect, helper cells appear to be competent in the production of maturation factors as well [12].…”

Section: Physiology Of B Cell Activation and Clonal Performancesmentioning

confidence: 99%

“…At least one type of BCGF is produced by T lymphocytes, and although definitive evidence is still lacking in this respect, helper cells appear to be competent in the production of maturation factors as well [12].…”

Section: Physiology Of B Cell Activation and Clonal Performancesmentioning

confidence: 99%

The Membrane Receptor Complex Regulating Induction and Clonal Expansion of Normal Murine B Lymphocytes

Forsgren¹,

Kleine²,

Pobor³

et al. 1984

Clinical Infectious Diseases

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Induction of resting B lymphocytes results from the interaction of competent ligands or helper cells with "triggering receptors." Subsequent clonal expansion and performance are thought to be regulated by the interaction of selective growth or maturation factors with specific receptors on induced B cells. A set of membrane molecules of B lymphocytes, including IgM, IgD, lA, IE, lipopolysaccharide receptors, receptors for Fe and C3b, and other non-immunoglobulin structures recognized by some antiidiotypic antibodies, display ligand-induced relationships. Functional studies also indicate that this group of molecules functions as a complex that regulates delivery of inductive signals, the expression of growth and maturation receptors, and/or the outcome of the interactions of these receptors with the corresponding factors.Network concepts [1] have radically altered classic perspectives of the immune system. Defense against infection is no longer the only or even the major aspect in immune physiology: the immune system is turned inward and includes images of all molecular patterns. No distinction can be made between the epitopes of "self' and "nonself." In spite of this profound conceptual revolution, some properties of bacterial products in their interaction with lymphocytes make it unescapable to conclude that the immune system started, at least in part, by being a protective, antiinfectious organ. The remnants of this evolutionary past are numerous and quite spectacular [2][3][4]. Perhaps the most widely analyzed is the ability of lipid A to stimulate a large fraction (10%-50%) of all B lymphocytes in the mouse.The mere consideration of this phenomenon is sufficient for us to conclude that "internal images" of lipid A do not exist in vertebrates and to segregate properties of lipid A from the universe of the epitope and the molecular basis of those reactions from that of antibody recognition. In fact it has been established that B lymphocyte reactivity toThe work summarized in this paper was supported in part by the Swedish Medical Research Council.We thank Ms. C. Bergman and Ms. J. Badella for typing the manuscript.Please address correspondence to Dr. Stina Forsgren, Department of Immunology, University of Urnea, S-901 85 Umea, Sweden. 524 lipid A is controlled by a locus on chromosome 4 [5, 6] that appears to determine the expression of membrane molecules that specifically bind lipid A and are competent to generate triggering signals [7]. The study of the biochemistry of those putative lipid A receptors has been haltered by the difficulty in preparing monospecific reagents. On the other hand, recent progress in the analysis of B cell activation, growth, and maturation provide new perspectives for the role of "triggering" or "mitogen" receptors in B cell physiology. We shall briefly discuss this progress here. Physiology of B Cell Activation and Clonal PerformancesThe analysis of B cell responses stimulated by helper T lymphocytes has revealed three distinct phases: (1) induction of resting B lymphocytes to a st...

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Distinct helper activities control growth or maturation of B lymphocytes

Cited by 21 publications

References 30 publications

B lymphocyte activation upon exclusive recognition of major histocompatibility antigens by T helper cells

B lymphocyte activation upon exclusive recognition of major histocompatibility antigens by T helper cells

The expression of a set of antibody variable regions in lipopolysaccharide‐reactive B cells at various stages of ontogeny and its control by anti‐idiotypic antibody

The Membrane Receptor Complex Regulating Induction and Clonal Expansion of Normal Murine B Lymphocytes

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