Phenotypic and functional characterization of a panel of cytotoxic murine NK cell clones that are heterogeneous in their enhancement of Ig secretion in vitro

Vos, Quirijn; Ortaldo, John R.; Conan-Cibotti, Michelle; Vos, Michele D.; Young, Howard A.; Anderson, S K; Witherspoon, Kim; Prager, Ilan; Snapper, Clifford M.; Mond, James J.

doi:10.1093/intimm/10.8.1093

Cited by 12 publications

(14 citation statements)

References 62 publications

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“…Direct interaction between B and NK cells under activated conditions are supported by several studies, particularly in mouse models (15)(16)(17)(18). Evidence from human studies suggests that NK cells and B cells can spontaneously interact in vitro, as demonstrated by conjugate formation and activation of the interacting cells (11).…”

Section: Cd2mentioning

confidence: 94%

Human B Cell Activation by Autologous NK Cells Is Regulated by CD40-CD40 Ligand Interaction: Role of Memory B Cells and CD5+ B Cells

Blanca

Bere

Young

et al. 2001

The Journal of Immunology

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NK cells are a subpopulation of lymphocytes characterized primarily by their cytolytic activity. They are recognized as an important component of the immune response against virus infection and tumors. In addition to their cytolytic activity, NK cells also participate either directly or indirectly in the regulation of the ongoing Ab response. More recently, it has been suggested that NK cells have an important role in the outcome of autoimmune diseases. Here, we demonstrate that human NK cells can induce autologous resting B cells to synthesize Ig, including switching to IgG and IgA, reminiscent of a secondary Ab response. B cell activation by the NK cell is contact-dependent and rapid, suggesting an autocrine B cell-regulated process. This NK cell function is T cell-independent, requires an active cytoplasmic membrane, and is blocked by anti-CD40 ligand (anti-CD154) or CD40-mIg fusion protein, indicating a critical role for CD40-CD40 ligand interaction. Depletion studies also demonstrate that CD5+ B cells (autoreactive B-1 cells) and a heterogeneous population of CD27+ memory B cells play a critical role in the Ig response induced by NK cells. The existence of this novel mechanism of B cell activation has important implications in innate immunity, B cell-mediated autoimmunity, and B cell neoplasia.

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Section: Cd2mentioning

confidence: 94%

Human B Cell Activation by Autologous NK Cells Is Regulated by CD40-CD40 Ligand Interaction: Role of Memory B Cells and CD5+ B Cells

Blanca

Bere

Young

et al. 2001

The Journal of Immunology

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“…Regarding immortalized NK lines, there are a few studies on generation of murine NK [85][86][87][88][89] and human NK [90] cell lines. Dr. Tian and coworkers recently summarized the NK cell lines in cancer immunotherapy [48].…”

Section: Remaining Challengesmentioning

confidence: 99%

Overcome the Impairment of NK Cells for Icon and Antibody Immunotherapy of Cancer

Hu¹

2013

JIBTVA

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Natural killer (NK) cells play an important role in innate immunity and in mediating antibody and Icon (an antibody-like factor VII/IgG1 Fc immunoconjugate, which, to our best knowledge, was the first therapeutic agent for dual targeting of both the tumor cells and tumor angiogenic endothelial cells) for cancer immunotherapy. However, a common yet often neglected observation and challenge in antibody immunotherapy is that NK cells are often impaired in cancer patients. Here we hypothesize that the impairment of NK cells significantly contributes to host resistance to antibody immunotherapy for cancer. In order for antibody and Icon to achieve their optimal therapeutic efficacy, we briefly reviewed the current strategies to enhance NK activity, including infusion of cytokines, vaccines or NK cells, and the use of dietary supplements. Moreover, from our point of view we identified some remaining challenges and propose to combine these NK-enhancing strategies with Icon or antibody to overcome NK impairment and ultimately to optimize the efficacy of Icon and antibody immunotherapy for cancer.

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“…While immunization of mice that have combined T and NK deficiency with TI-2 antigens results in normal IgM antibody responses (239) (Q. Vos, J. J. Mond, unpublished results), Yuan and co-wokers have shown that activation of NK activity by administration of polyinosinic-polycytidylic acid (225) or tumor cells (240) can modulate in vivo TI-2 responses. A series of studies has described the ability of NK to stimulate Ig secretion in vitro (241)(242)(243)(244)(245)(246)(247). We have shown that NK-cell secretion of IFN-g is a critical parameter for the induction of Ig secretion in B cells stimulated with ad-dex and IL-2, and that the level of modulation of Ig secretion by a panel of murine NK clones correlates with their level of IFN-g secretion (244)(245)(246)(247).…”

Section: Modulation Of Ti-2 Responses By Nk Cellsmentioning

confidence: 99%

“…A series of studies has described the ability of NK to stimulate Ig secretion in vitro (241)(242)(243)(244)(245)(246)(247). We have shown that NK-cell secretion of IFN-g is a critical parameter for the induction of Ig secretion in B cells stimulated with ad-dex and IL-2, and that the level of modulation of Ig secretion by a panel of murine NK clones correlates with their level of IFN-g secretion (244)(245)(246)(247). In addition, we have preliminary evidence for NK secretion of additional B-cell stimulatory cytokines, since B-cell stimulation in the presence of supernatants of some of our NK clones showed a kinetics of Ig induction and an Ig-isotype pattern that could not be induced by purified IFN-g itself (Q. Vos, J. J. Mond, unpublished results).…”

Section: Modulation Of Ti-2 Responses By Nk Cellsmentioning

confidence: 99%

B‐cell activation by T‐cell‐independent type 2 antigens as an integral part of the humoral immune response to pathogenic microorganisms

Vos

Lees²,

Wu³

et al. 2000

Immunological Reviews

391

115

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Antigens that are expressed on the surface of pathogens in an organized, highly repetitive form can activate specific B cells by cross-linking of antigen receptors in a multivalent fashion. B cells respond to these multivalent antigens in the absence of MHC class II-restricted T-cell help by a mechanism that depends on the expression of a functional Bruton's tyrosine kinase (Btk). Accordingly, this class of immunogens has been designated T-cell-independent type 2 (TI-2) antigens. The unique properties of the B-cell response to TI-2 antigens are critically dependent on the formation of a small number of antigen receptor clusters, each of which contains approximately 10 to 20 antigen-bound membrane Ig (mIg) molecules. These clusters induce local membrane association of multiple activated Btk molecules, which results in long-term mobilization of intracellular ionized calcium. Such persistent calcium fluxes efficiently recruit transcription factors and thereby induce T-cell-independent B-cell activation and proliferation. While this first signal of multivalent mIg cross-linking can induce B-cell proliferation, we propose that a second signal is required for a TI-2 Ig secretory response. We have found that engagement of members of the Toll-like receptor (TLR) family could provide second signals that selectively induce Ig secretion in B cells that were activated by multivalent, but not by bivalent, antigen receptor engagement. This finding demonstrates a general mechanism by which TLRs recognize molecular motifs on the surface of pathogens and provide the TI-2-activated B cell with a second signal. In addition, TLR-dependent recognition of these non-self motifs by cells of the innate immune system can induce these cells to provide alternative and/or additional second signals in the TI-2 response. The complement system provides another link between the B cell and the innate immune system, and facilitates the mIg signal transduction by recruitment of CD21 in the immune response. Thus, the TI-2 response provides the host with a combination of "the best of both worlds": the recruitment of the fine specificity of the adaptive immune response and the utilization of both the speed of the innate immune system and the wealth of cytokines produced by its member cells upon stimulation by pathogenic organisms or their products. By combining these two pathways, the TI-2 response enables the host to rapidly produce antigen-specific Ig effector molecules that can be secreted at a sufficient rate to keep up with the rapid multiplication of invading infectious microorganisms, and will also prevent the intracellular spreading of a significant part of this population.

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Phenotypic and functional characterization of a panel of cytotoxic murine NK cell clones that are heterogeneous in their enhancement of Ig secretion in vitro

Cited by 12 publications

References 62 publications

Human B Cell Activation by Autologous NK Cells Is Regulated by CD40-CD40 Ligand Interaction: Role of Memory B Cells and CD5+ B Cells

Human B Cell Activation by Autologous NK Cells Is Regulated by CD40-CD40 Ligand Interaction: Role of Memory B Cells and CD5+ B Cells

Overcome the Impairment of NK Cells for Icon and Antibody Immunotherapy of Cancer

B‐cell activation by T‐cell‐independent type 2 antigens as an integral part of the humoral immune response to pathogenic microorganisms

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