Mechanism and Regulation of Immunoglobulin Isotype Switching

Coffman, Robert L.; Lebman, Deborah A.; Rothman, Paul B.

doi:10.1016/s0065-2776(08)60536-2

Cited by 508 publications

(319 citation statements)

References 223 publications

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“…More importantly, switching adjuvants did not change the outcome of the antibody responses generated by the adjuvant used initially. The presence of IgG1 antibody is indicative of a Th2-type immune response, whereas IgG2a is indicative of a Th1-type immune response [44][45][46][47][48]. The results of the present study show that, in both strains of mice, switching from Alum to Quil A did not change the Th2 phenotype of antibody responses, although it reduced the IgG1/IgG2a ratio (Fig.…”

Section: Discussionmentioning

confidence: 52%

Prototype Alzheimer's disease epitope vaccine induced strong Th2-type anti-Aβ antibody response with Alum to Quil A adjuvant switch

Ghochikyan

Mkrtichyan

Petrushina

et al. 2006

Vaccine

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Section: Discussionmentioning

confidence: 52%

Prototype Alzheimer's disease epitope vaccine induced strong Th2-type anti-Aβ antibody response with Alum to Quil A adjuvant switch

Ghochikyan

Mkrtichyan

Petrushina

et al. 2006

Vaccine

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“…Therefore, we studied the effects of anti-CD40 MoAbs, which can replace activated CD4 + T cells expressing CD40L in vitro [5,37,38], on B-cell differentiation in patients with CVI. Anti-CD40 MoAbs alone had no effect on the numbers of Ig-secreting cells in patients or controls, which is consistent with earlier studies [5,38,39]. When cultured in the presence of IL-2, IL-4 or IL-13, anti-CD40 MoAbs induced low levels of Ig-secreting cells ( Table 3).…”

Section: Resultsmentioning

confidence: 99%

IL‐4 Synergizes with IL‐10 and Anti‐CD40 MoAbs to Induce B‐Cell Differentiation in Patients with Common Variable Immunodeficiency

Punnonen¹,

Kainulainen

Ruuskanen

et al. 1997

Scand J Immunol

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Punnonen J, Kainulainen L, Ruuskanen O, Nikoskelainen J, Arvilommi H. IL-4 Synergizes with IL-10 and Anti-CD40 MoAbs to Induce B-Cell Differentiation in Patients with Common Variable Immunodeficiency. Scand J Immunol 1997;45:203-212 In the present study the phenotype and function of lymphocytes from patients with common variable immunodeficiency (CVI) were studied. Five out of 12 patients had abnormally low proportion of CD4 + T cells, but PBMC of these patients were capable of proliferating in response to polyclonal T-cell mitogens or PPD antigen. The phenotype of patients' B cells, as determined by expression of CD10, CD19 and CD34, was comparable to that of healthy controls. IL-4 and anti-CD40 MoAbs induced moderate B-cell differentiation in PBMC derived from patients with CVI, but the frequencies of Ig-secreting cells were generally at levels spontaneously observed in healthy controls. IL-10 was completely ineffective in inducing IgG-secreting cells in cultures of PBMC derived from patients with CVI even in the presence of anti-CD40 MoAbs, whereas high frequencies of Ig-secreting cells were induced under similar condition in cultures of PBMC derived from healthy controls. Importantly, when IL-4 was added to cultures stimulated with anti-CD40 MoAbs and IL-10, a very strong synergistic effect on the numbers of Ig-secreting cells and the levels of Ig secretion was observed in PBMC from both patients and controls. Moreover, the frequencies of Ig-secreting cells after activation with anti-CD40 MoAbs, IL-4 plus IL-10 in PBMC from some patients were comparable to those observed in PBMC from healthy controls. Taken together, these results indicate that B cells from patients with CVI have impaired capacity to differentiate into Ig-secreting cells in response to IL-10 and anti-CD40 MoAbs, and that this unresponsiveness can be restored by exogenous IL-4 in a proportion of the patients.

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“…Isotype selection in turn is a property of activated B cells and is controlled by two variables: 1) the cytokines to which the activated B cells are exposed and 2) the mode of B cell activation, especially whether T-dependent (TD) or T-independent (TI) [1][2][3]. In studies of murine B cell responses, three cytokines have been unequivocally shown to initiate the molecular events associated with switching: IL-4, IFN-c and TGF-b [1,2]. IL-4 induces switching to IgG1 and IgE, IFN-c induces IgG2a and TGF-b is a switch factor for IgG2b and IgA.…”

Section: Introductionmentioning

confidence: 99%

Decision criteria for resolving isotype switching conflicts by B cells

2005

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Isotype switching by B cells is highly regulated by a group of cytokines including IL-4, IFN-c and TGF-b. A B cell can only express one isotype at a time; however, during an immune response it may be exposed to combinations of stimuli that provide it with conflicting switching instructions. To determine how such cytokine-induced isotype switch conflicts would be resolved, the responses of B cells exposed to multiple cytokines were investigated. To eliminate complications arising from simultaneous effects of switching cytokines on proliferation, division number was used as a reference framework to monitor switching rate. The results show a clear hierarchy in which IFN-c is dominant over IL-4, and both IL-4 and IFN-c are dominant over TGF-b. These studies reveal how B cells possess a set of logical decision criteria for dealing with pathogens that invoke a range of different stimuli.

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Mechanism and Regulation of Immunoglobulin Isotype Switching

Cited by 508 publications

References 223 publications

Prototype Alzheimer's disease epitope vaccine induced strong Th2-type anti-Aβ antibody response with Alum to Quil A adjuvant switch

Prototype Alzheimer's disease epitope vaccine induced strong Th2-type anti-Aβ antibody response with Alum to Quil A adjuvant switch

IL‐4 Synergizes with IL‐10 and Anti‐CD40 MoAbs to Induce B‐Cell Differentiation in Patients with Common Variable Immunodeficiency

Decision criteria for resolving isotype switching conflicts by B cells

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