Characterization of CD40‐Dependent Immunoglobulin Class Switching

Abstract

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.

Induced Expression of Murine γ2a by CD40 Ligation Independently of IFN-γ

“…Our results using CD40L-expressing Sf21 cells as a B cell activator in tissue culture differ somewhat from results using agonistic anti-CD40 Abs (33). Anti-CD40 Abs have not been found to induce germline or postswitch transcripts of the ␥2a gene (29,30,33).…”

Decision criteria for resolving isotype switching conflicts by B cells

“…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.…”

Differential Regulation of Mouse Germline Ig γ1 and ε Promoters by IL-4 and CD40

“…CD40L or Ab to CD40 synergizes with IL-4 to further induce GL ⑀ and mouse ␥1 transcripts in cultured mouse splenic B cells (28 -32). In the absence of IL-4, CD40 signaling induces modest levels of GL ␥1 and ⑀ transcripts, but ␥1 transcripts appear to be more inducible than ⑀ transcripts (18,31,32).…”

“…Furthermore, T cell contact help, primarily mediated by CD40-CD40 ligand (L) interaction, is important for B cell activation, proliferation, and isotype switching during T-dependent immune responses (14 -16). Ab to CD40 or CD40L synergizes with IL-4 to induce switching to IgG1 and IgE in cultured mouse splenic B cells (17,18) and expression of certain IgG subclasses and IgE in cultured human B cells (19,20). Although IL-4 induces both IgG1 and IgE, these isotypes differ in their dependence on IL-4.…”