Surface immunoglobulins of lipopolysaccharide‐stimulated spleen cells The behaviour of IgM, IgD and IgG

Bourgois, Alain; Kitajima, Kumiko; Hunter, I.R.; Askonas, Brigitte A.

doi:10.1002/eji.1830070307

Cited by 85 publications

(41 citation statements)

References 14 publications

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“…34,35 Furthermore, the reduced smIgD-to-smIgM ratio reported here may also reflect activation-induced modulation since mature B cells that coexpress IgM and IgD down-regulate IgD upon BCR signaling. 36,37 Indeed, B-CLL cells from most patients exhibit diminished levels of surface immunoglobulin. [38][39][40][41] Of interest is the reduced expression of CD22 and CD32 (Figures 2-3; Bourgois et al 36 ; Merson and Brochier 39 ), molecules that participate in the negative regulation of BCR-mediated [42][43][44][45] and CD38-mediated 46 responses.…”

Section: B-cll Cells From All Cases Display An Activated Surface Membmentioning

confidence: 99%

B-cell chronic lymphocytic leukemia cells express a surface membrane phenotype of activated, antigen-experienced B lymphocytes

Damle

2002

Blood

294

219

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B-cell chronic lymphocytic leukemia (B-CLL. Indeed, the view that B-CLL cells are antigen-naive and resting is consistent with their appearance as small lymphocytes with high nuclear-to-cytoplasmic ratios 2 and their surface membrane coexpression of immunoglobulin M (IgM) and IgD, which usually marks virgin B cells. 3 Nonetheless, the concepts that B-CLL cells are homogeneous and similar among patients and that they resemble antigen-naive and resting B cells are currently being called into question. For example, the documentation of somatic mutations in the leukemic lymphocytes of greater than 50% of these patients [4][5][6][7] indicates that B-CLL cells are not necessarily similar among patients and that the disease is not homogeneous in this respect. In fact, B-CLL cases can be divided into at least 2 subgroups on the basis of the presence or absence of significant numbers of V gene mutations; these subgroups identify patients that follow strikingly dissimilar clinical courses. 8,9 Since the induction of immunoglobulin V gene mutations requires cellular activation and maturation induced by antigen receptor engagement, 10,11 B-CLL cells with immunoglobulin V gene mutations resemble antigen-experienced B cells that at one point in their evolution were activated and therefore are not antigen-naive. On the basis of this reasoning, the question arises as to whether B-CLL cells that exhibit immunoglobulin V genes with germ line-like sequences are indeed resting and antigen-naive or whether they also represent B cells that were stimulated out of the resting state by antigen but that did not accumulate mutations.In addition, other data suggest that in vivo activation, albeit abortive, can occur in B-CLL. For example, B-CLL cells can express elevations of cyclin D2 without increases of the other cyclins that follow in cell cycle progression. 12 Furthermore, B-CLL cells can exhibit constitutive translocation of nuclear factor of activated T cells (NF-ATp) 13 and phosphorylation of signal transducer and activator of transcription 1 (STAT-1) and STAT-3. 14 Finally, most B-CLL cells express CD23, a cell surface marker acquired after B-cell activation. [15][16][17][18] These findings suggest that certain B-CLL cells or their precursors may have been triggered and may have attempted to traverse the cell cycle, and may therefore not be resting or antigen-naive.To examine further the possibility that the leukemic cells from all B-CLL cases are antigen-experienced and exist in an activated Patients, materials, and methods Patients and healthy donorsThe Institutional Review Boards of North Shore University Hospital (Manhasset, NY) and Long Island Jewish Medical Center (New Hyde Park, NY) approved these studies. Informed consent was provided by all participants in accordance with the Declaration of Helsinki. A total of 61 cases diagnosed as B-CLL were studied. Laboratory data on a subset of these cases have been reported earlier. 3,7,8 Patients were selected for the present study on the basis of the availability of DNA sequences...

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Section: B-cll Cells From All Cases Display An Activated Surface Membmentioning

confidence: 99%

B-cell chronic lymphocytic leukemia cells express a surface membrane phenotype of activated, antigen-experienced B lymphocytes

Damle

2002

Blood

294

219

View full text Add to dashboard Cite

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“…Marginal-zone B cells express high levels of IgM but down-regulate IgD on the surface [2,3]. After activation by LPS, B cells rapidly down-regulate the expression of IgD, but not IgM [4,5].…”

Section: Introductionmentioning

confidence: 99%

IgD⁺IgM^– B cells mount immune responses that exhibit altered antibody repertoire

Han

Zhang

et al. 2004

Eur J Immunol

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IgM and IgD expression during B cell development and differentiation is strictly and developmentally controlled. Although studies have suggested subtle differences in B cell activation, tolerance, and affinity maturation when antigens ligate cell membrane IgM or IgD, the mechanisms that may explain these differences remain unknown and no drastic differences in immune responses have been reported in mice whose B cells selectively lack IgM or IgD. We now show that the antibody repertoire in IgM -/-mice is dramatically altered during the primary response to phosphorylcholine. In IgM -/-mice, B cells that are activated and differentiate into antibody-forming cells and germinal center B cells express V H genes other than the T15 genes that dominate in wild-type mice. The kinetics of the antigen-specific IgD primary antibody response in IgM -/-mice appears similar to that of IgG, but not to that of IgM in wildtype mice. Thus, our studies demonstrate that differences in the roles played by IgM and IgD in regulating the responsiveness and differentiation of B lymphocytes can have major biological consequences during adaptive immune responses.

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“…These cells are predominantly B cells in peripheral lymphoid tissues and are considered mature, resting B cells. Several recent studies have shown that mature B cells bearing IgM and IgD lose IgD from their surface when stimulated with mitogens or antigens and later differentiate into IgM-, IgG-, and IgA-secreting cells (20,22,23). Thus, if the differentiation of that population of B cells was suppressed by anti-IgM or anti-IgD antibodies, not only IgM but also IgG production could be suppressed.…”

Section: Discussionmentioning

confidence: 99%

Relationship between reduced b cell susceptibility to igm antibodies and reduced igd‐bearing b cells in patients with systemic lupus erythematosus

Suzuki

Sakurami²,

Imura

1982

Arthritis & Rheumatism

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Peripheral blood lymphocytes from 14 patients with systemic lupus erythematosus, 5 patients with rheumatoid arthritis, and 10 normal subjects were cultured for 7 days with or without anti‐IgM or anti‐IgD antibodies, and IgG‐ and IgM‐secreting cells were assayed by reverse hemolytic plaque assay. Surface immunoglobulin (Ig) isotypes on peripheral blood B cells were also examined by a direct anti‐Ig resetting reaction. In normal subjects and rheumatoid arthritis patients, the spontaneous development of IgG‐ and IgM‐secreting cells was markedly suppressed by anti‐IgM or anti‐IgD antibodies. Over 50% of peripheral blood B cells were IgD‐ and/or IgM‐bearing cells in normal subjects and in most patients with rheumatoid arthritis. In lupus patients, however, the suppression of IgG and IgM production by anti‐IgM or anti‐IgD antibodies was remarkably reduced, especially in the active stage. Furthermore, the percentage of IgD‐bearing cells in peripheral blood B cells was remarkably reduced, especially in patients with active disease. There was a good correlation between reduced susceptibility of B cells to anti‐IgM antibody‐mediated suppression and reduced percentage of IgD‐bearing cells in lupus patients.

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Surface immunoglobulins of lipopolysaccharide‐stimulated spleen cells The behaviour of IgM, IgD and IgG

Cited by 85 publications

References 14 publications

B-cell chronic lymphocytic leukemia cells express a surface membrane phenotype of activated, antigen-experienced B lymphocytes

B-cell chronic lymphocytic leukemia cells express a surface membrane phenotype of activated, antigen-experienced B lymphocytes

IgD⁺IgM^– B cells mount immune responses that exhibit altered antibody repertoire

Relationship between reduced b cell susceptibility to igm antibodies and reduced igd‐bearing b cells in patients with systemic lupus erythematosus

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Surface immunoglobulins of lipopolysaccharide‐stimulated spleen cells The behaviour of IgM, IgD and IgG

Cited by 85 publications

References 14 publications

B-cell chronic lymphocytic leukemia cells express a surface membrane phenotype of activated, antigen-experienced B lymphocytes

B-cell chronic lymphocytic leukemia cells express a surface membrane phenotype of activated, antigen-experienced B lymphocytes

IgD+IgM– B cells mount immune responses that exhibit altered antibody repertoire

Relationship between reduced b cell susceptibility to igm antibodies and reduced igd‐bearing b cells in patients with systemic lupus erythematosus

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IgD⁺IgM^– B cells mount immune responses that exhibit altered antibody repertoire