Cutting Edge: γδ T Cells Provide Help to B Cells with Altered Clonotypes and Are Capable of Inducing Ig Gene Hypermutation

Zheng, Biao; Marinova, Ekaterina; Han, Jin; Tan, Tse‐Hua; Han, Shuhua

doi:10.4049/jimmunol.171.10.4979

Cited by 21 publications

(16 citation statements)

References 27 publications

(35 reference statements)

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“…These data further support the notion that ␥␦ T cells are endowed with more sophisticated functions than simply providing a first-line defense against pathogens or self-induced stress antigens in the peripheral tissues. Mouse models have confirmed that ␥␦ T cells do provide help to adaptive immune responses by promoting the formation of germinal centers, the somatic hypermutation of B cells, 26 and by positively regulating superantigen-specific immune responses mediated by ␣␤ T cells. 27 In conclusion, our results indicate that it is possible to quickly generate large numbers of activated ␥␦ T cells with effector and costimulatory activities by short-term incubation with iDCs/mDCs pulsed with the appropriate antigens.…”

Section: Discussionmentioning

confidence: 92%

Enhanced ability of dendritic cells to stimulate innate and adaptive immunity on short-term incubation with zoledronic acid

Fiore

Castella

Nuschak

et al. 2007

Blood

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Section: Discussionmentioning

confidence: 92%

Enhanced ability of dendritic cells to stimulate innate and adaptive immunity on short-term incubation with zoledronic acid

Fiore

Castella

Nuschak

et al. 2007

Blood

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“…In TD B cell responses, the latter signals are probably predominantly provided by Th cells, but TLRs and other molecules capable of inducing signaling pathways involved in B cell growth and survival undoubtedly contribute as well. We and others have shown that GCs can be transiently induced in the apparent absence of T cell help (46,47), and very small numbers of T cells of various subtypes are sufficient to drive efficient GC, but not anamnestic AFC development (48,49).…”

Section: Discussionmentioning

confidence: 99%

Quantitatively Reduced Participation of Anti-Nuclear Antigen B Cells That Down-Regulate B Cell Receptor during Primary Development in the Germinal Center/Memory B Cell Response to Foreign Antigen

Alabyev

Rahman

Manser

2007

The Journal of Immunology

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The peripheral B cell compartment contains high levels of “polyreactivity” including autospecificities. We have described a pathway that certain autoreactive B cells may take in gaining stable access to the foreign Ag-responsive peripheral compartment. This pathway was revealed in mice expressing a targeted Ig H chain transgene encoding BCRs with “multireactivity” for the hapten arsonate and DNA-based autoantigens. B cells expressing such BCRs develop to mature follicular phenotype and locale, and are not short-lived. These B cells express very low levels of BCR, indicating that they are not “ignorant” of self Ag, but do not display features of anergy in in vitro assays. Nonetheless, a variety of states of lymphocyte anergy has been described, and some may only be manifested in vivo. As such, we analyzed the ability of these B cells to participate in a T cell-dependent immune response to arsonate in vivo. These B cells mount an early primary response similar to control B cells, including homing to follicles, migration to the T-B interface, and induction of costimulatory molecules, proliferation, differentiation to AFCs, class switching, and entry into GCs and somatic hypermutation. Nonetheless, these B cells display reduced participation in the latter stages of the GC response and in the anamnestic AFC response. In total, these data suggest that while the autoreactivity of this type of B cell does not result in anergy, the ability of such B cells to participate in a cross-reactive immune response to foreign Ag is compromised.

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“…Using a model of pulmonary allergic inflammation, decreased production of IgE and IgG 1 was seen in mice lacking ␥␦ T cells compared with WT mice (12). The ␥␦ T cells have also been shown to directly induce germinal center formation and Ig hypermutation (13). Interestingly, even though the ␥␦ T cells expressing CD4 account for only 5-10% of all ␥␦ cells, it is this subset that appears to be responsible for inducing germinal centers (14).…”

Section: T Cell Development ͉ T Cell Differentiation ͉ T Cell Signalingmentioning

confidence: 99%

Tec kinase Itk in γδT cells is pivotal for controlling IgE production in vivo

Felices

Yin

Kosaka

et al. 2009

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

113

145

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T cell development ͉ T cell differentiation ͉ T cell signaling T he Tec family tyrosine kinase Itk is important for signaling downstream of the T cell receptor (1). In particular, Itkdeficient T cells have defects in phospholipase C-␥ (PLC-␥) phosphorylation, calcium mobilization, mitogen-activated protein kinase (MAP kinase) activation, and AP-1 and nuclear factor of activated T cells (NFAT) activation after T cell receptor (TCR) stimulation. Itk is also critical for conventional ␣␤ T cell development, selection, and function. Of particular importance, Itk signaling regulates CD4 ϩ T helper cell differentiation, playing a key role in the development of Th2 responses (2). Based on this welldocumented defect of Itk Ϫ/Ϫ mice in generating Th2 effector responses and cytokine production, it was surprising to discover that these mice had spontaneously elevated levels of serum IgE (3, 4), as B cell isotype switching to IgE is highly dependent on Th2 cytokines IL-4 and IL-13 (5). As our previous studies had indicated that Itk Ϫ/Ϫ ␣␤ TCR ϩ NKT cells (referred to as ␣␤ NKT cells) were also highly defective in producing effector cytokines such as IL-4 (6), we considered the possibility that ␥␦ TCR ϩ NKT cells were the major source of Th2 cytokines in Itk Ϫ/Ϫ mice.The ␥␦ T cells are a highly conserved subset of T cells that constitutes 1-5% of the lymphocytes in the blood and peripheral organs of mice but can account for up to 50% of the lymphocytes in the mucosal epithelia. As with other subsets of ''innate'' T cells, ␥␦ T cells express memory cell surface markers (7), and are capable of rapidly secreting effector cytokines (8). Among the many functions attributed to ␥␦ T cells, a great deal of recent interest has focused on their ability to modulate adaptive immune responses, specifically the humoral response (9).A variety of studies have indicated that ␥␦ T cells are able to provide help for B cell responses. Initial studies performed in mice lacking ␣␤ T cells showed that B cell expansion, differentiation, and secretion of 'T-dependent' antibody isotypes, IgE, and IgG 1 , were all intact in these mice (10). Furthermore, TCR␤ Ϫ/Ϫ mice challenged repeatedly with parasitic infections could produce germinal centers and generate increased antibody production (11). Using a model of pulmonary allergic inflammation, decreased production of IgE and IgG 1 was seen in mice lacking ␥␦ T cells compared with WT mice (12). The ␥␦ T cells have also been shown to directly induce germinal center formation and Ig hypermutation (13). Interestingly, even though the ␥␦ T cells expressing CD4 account for only 5-10% of all ␥␦ cells, it is this subset that appears to be responsible for inducing germinal centers (14). Human ␥␦ T cells have also been found in germinal centers; these cells were found to up-regulate B cell costimulatory molecules such as CD40L, OX40, CD70, and inducible costimulatory molecule (ICOS) in response to TCR stimulation (15, 16). Together, these data indicate that ␥␦ T cells can promote, either directly or indirectly, th...

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Cutting Edge: γδ T Cells Provide Help to B Cells with Altered Clonotypes and Are Capable of Inducing Ig Gene Hypermutation

Cited by 21 publications

References 27 publications

Enhanced ability of dendritic cells to stimulate innate and adaptive immunity on short-term incubation with zoledronic acid

Enhanced ability of dendritic cells to stimulate innate and adaptive immunity on short-term incubation with zoledronic acid

Quantitatively Reduced Participation of Anti-Nuclear Antigen B Cells That Down-Regulate B Cell Receptor during Primary Development in the Germinal Center/Memory B Cell Response to Foreign Antigen

Tec kinase Itk in γδT cells is pivotal for controlling IgE production in vivo

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