B-Cell Activation (original) (raw)
In-vitro analyses of mechanisms of B-cell development
Seminars in Immunology, 1995
B-cell lymphopoiesis in vivo is vq complex due to the influences of cooperating cells, qtokines and other receptor-ligand interactions which appear to occur develojnnentally at daffment cellular stages. Therefore in-vitro models will help to unravel this complex situation. Here, we review our and others' work on in-vitro models of B-cell development. The role of stromal cells, cytokines, surrogate light chain and wducts of rearranged Ig-loci in the o!evela,bmentally different cellular stages will be discussed.
Blood, 1992
Newly formed B lymphocytes are a population of rapidly renewed cells in the bone marrow of mammals and their steady state production presumably depends on a cascade of regulatory cells and cytokines. Although considerable information has been forthcoming about the role of interleukin-7 (IL-7) in potentiating pre-B-cell proliferation, few studies have addressed the possibility that multiple cytokines are involved in the progression of early events in cellular differentiation and proliferation in this hematopoietic lineage. Our laboratory previously described pre-B-cell differentiation mediated by the bone marrow stromal cell line S17. In this study, we further delineate the role of stromal cells in differentiation and proliferation of pre-B cells. These experiments show that the stromal cell line S17 potentiates the proliferative effect of IL-7 on B-lineage cells and that this S17-derived potentiator can be replaced with recombinant kit-ligand (KL). Our results further show that pre-...
Regulation of B-Lymphocyte Activation, Proliferation, and Differentiation
Annals of the New York Academy of Sciences, 1987
Lymphocyte growth and differentiation are controlled by signals resulting from the interaction of antigen and cellular products, such as lymphokines, with specific cell membrane receptors. Resting B lymphocytes can be activated by low concentrations (l-5 &ml) of antibodies to membrane IgM, which is the B-lymphocyte receptor for antigen. The binding of anti-IgM to B cells causes a rapid increase in intracellular free calcium concentration ([Ca"]i), in inositol phosphate concentration, and in protein kinase activity. Moreover, the effects of anti-IgM on B cells are mimicked by the combined use of calcium ionophores and phorbol esters. Since phorbol esters activate protein kinase c, this suggests that the increase in [Ca*']i and in phosphatidylinositol metabolism stimulated by anti-&M are critical events in B-cell activation. The entry into S phase of B cells stimulated with anti-IgM depends on the action of a T-cell-derived factor designated B-cell stimulatory factor (BSF)-1. This is a 20,000-Da protein which is a powerful inducer of class II major histocompatibility complex molecules. Although an important cofactor for B-cell proliferative responses to anti-IgM, its major locus of action is on resting B cells. B cells stimulated with anti-IgM and BSF-1 do not synthesize secretory IgM. However, if two additional T-cellderived factors, B 15 I-TRF and interleukin-2, are added to cultures, a substantial proportion of stimulated B cells produce secretory IgM. BSF-1 has also been shown to participate in the "switch" in Ig class expression. Resting B cells cultured with lipopolysaccharide will switch to IgG, secretion in the presence of purified BSF-1.
Sites of B-cell activation in vivo
Current Opinion in Immunology, 1993
Novel techniques have made possible in situ analyses of the lymphocyte populations responding to antigen. In the spleen, antigen-specific T and B cells are first observed in the periarteriolar lymphoid sheath. Following conjugate formation between specific T and B lymphocytes, B-cell proliferation and differentiation takes place in two distinct sites, the periarteriolar lymphoid sheath-associated foci and germinal centers.
Journal of Immunology, 1998
Germinal center responses to two analogous peptides, PS1CT3 and G32CT3, that differ in sequence only at one position within the B cell epitopic region were examined. In comparison with peptide PS1CT3, peptide G32CT3 elicited a poor germinal center response. By demonstrating equal facility of immune complexes with IgM and IgG Ab isotypes to seed germinal centers, we excluded differences in isotype profiles of early primary anti-PS1CT3 and anti-G32CT3 Ig as the probable cause. Quantitative differences in germinal center responses to the two peptides were also not due to either qualitative/quantitative differences in T cell priming or variation in the frequency of the early Ag-activated B cells induced. Rather, they resulted from qualitative differences in the nature of B cells primed. Analysis of early primary anti-PS1CT3 and anti-G32CT3 IgMs revealed that the latter population was of a distinctly lower affinity, implying the existence of an Ag affinity threshold that restricts germinal center recruitment of G32CT3-specific B cells. The impediment in anti-G32CT3 germinal center initiation could be overcome by making available an excess of Ag-activated Th cells at the time of immunization. This resulted in the appearance of a higher affinity population of G32CT3-specific B cells that, presumably, are now capable of seeding germinal centers. These data suggest that the strength of a germinal center reaction generated is Ag dependent. At least one regulatory parameter represents the quality of B cells that are initially primed.
Experimental Hematology, 2007
Objective. The role of interleukin (IL)-7 in human B lymphopoiesis is still controversial. We used an in vitro culture system to verify involvement of IL-7 in development of human pro-B cells from hematopoietic stem cells. Materials and Methods. Human CD34 + bone marrow cells were cultured for 4 weeks on MS-5 mouse stromal cells to induce pro-B cells. Expression of IL-7 receptor a or other B-cell differentiation marker genes on cultured human CD34 + bone marrow cells was investigated by reverse transcription polymerase chain reaction (RT-PCR). Colony assay of human CD34 + bone marrow cells was also performed to determine the effect of IL-7 on colony-forming ability. Neutralizing antibody or reagent that eliminates the effect of IL-7 was added to the culture system, and the number of pro-B cells induced was estimated by flow cytometry. Results. RT-PCR analysis revealed mRNA expression of IL-7 receptor a as well as B-cell differentiation marker genes in not only CD19 + pro-B cells but also CD19 L CD33 L cells induced from CD34 + bone marrow cells after cultivation for 4 weeks on MS-5 cells. Addition of antimouse IL-7 antibody, anti-human IL-7 receptor a antibody, or JAK3 kinase inhibitor reduced the number of pro-B cells induced, demonstrating that elimination of IL-7 reduces pro-B-cell development. Addition of anti-mouse IL-7 antibody emphasized the colony-forming ability of burst-forming unit erythroid cells.