Mitogen- and IL-4-regulated expression of germ-line Ig γ2b transcripts: Evidence for directed heavy chain class switching

Lutzker, Stuart; Rothman, Paul B.; Pollock, Roberta R.; Coffman, Robert L.; Alt, Frederick W.

doi:10.1016/0092-8674(88)90379-0

Cited by 271 publications

(127 citation statements)

References 47 publications

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“…This result is in agreement with previous findings that IL-4 inhibits the secretion of IgG2b and IgG3 and the production of c2b and c3 germline transcripts [16][17][18][19][20][21][22][23][24][25]. IL-4 was also found to inhibit the division-linked rate of switching to IgA.…”

Section: Discussionsupporting

confidence: 82%

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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Section: Discussionsupporting

confidence: 82%

Decision criteria for resolving isotype switching conflicts by B cells

2005

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“…Furthermore, we show that CD40 ligation stimulates GL ␥2b, but not ␥2a or ␣ transcripts. The ␥2b response was profoundly suppressed when IL-4 was added, in a way similar to stimulation by LPS plus IL-4 [47]. We found that GL ␥3 transcripts were expressed at equally high levels in unstimulated as in anti-CD40-stimulated B cells.…”

Section: Discussionmentioning

confidence: 66%

Characterization of CD40‐Dependent Immunoglobulin Class Switching

et al. 1999

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Ström L, Laurencikiené J, Miskiniené A, Severinson E. Characterization of CD40-Dependent Immunoglobulin Class Switching. Scand J Immunol 1999;49;523-532 Previous studies have shown that signalling via CD40 together with cytokines stimulates immunoglobulin (Ig) class switching in B cells. This process includes induction of germline (GL) transcripts and switch recombination. Using an agonistic rat anti-mouse CD40 monoclonal antibody (MoAb), we investigated the role of CD40 signalling in these molecular events. We found that stimulation of murine B cells induced high steady-state levels of germline ␥1, ␥2b and low levels of ⑀ transcripts. No detectable ␥2a or ␣RNA were found and the level of ␥3 transcripts was high both in stimulated and unstimulated cells. Although cells treated with anti-CD40 MoAb had high levels of GL ␥1 and ␥3 transcripts, we failed to detect switching to IgG1 or IgG3. However, anti-CD40 MoAb-stimulated cells increased expression of IgG2b. Interestingly, anti-CD40 plus interleukin (IL)-5 induced switching to IgG1. Previous work has demonstrated that CD40 signalling, but not lipopolysaccharide (LPS), induces the ␥1 promoter and that NF-B motifs are important. We show here that both LPS and anti-CD40 activated NF-B proteins binding to the ␥1 promoter. The bound NF-B complexes were different with regard to total concentration and subunit composition. In the light of our data, the mechanism of CD40-mediated Ig class switching is discussed.

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“…12 and 13 and unpublished data), T-bet likely regulates class switching via control of germline transcripts (Figs. 4-7), which have been implicated strongly as a prerequisite to isotype-switch recombination (36)(37)(38)(39)(40). Alternatively, T-bet may participate in mediating accessibility of the IgG locus to transcriptional or recombinatorial factors, as it does for IFN-␥ in CD4 T cells (13).…”

Section: Resultsmentioning

confidence: 99%