IL-4 upregulates Igα and Igβ protein, resulting in augmented IgM maturation and B cell receptor-triggered B cell activation.

IL-4 is critical for optimal B cell activation and germinal center B cell expansion in T-dependent immune responses; however, the underlying mechanism remains elusive. In the current study, we found that primary B cells express little Ig alpha and Ig beta protein despite substantial levels of mRNA. IL-4 markedly upregulates Ig alpha and Ig beta protein expression that requires STAT6. Elevated Ig alpha and Ig beta protein form heterodimers that associate with IgM and significantly promote IgM maturation and surface IgM expression, resulting in amplified BCR-initiated signaling that is Lyn dependent. In vivo, we found that pregerminal center B cells express upregulated Ig alpha, Ig beta, and surface IgM expression, in conjunction with elevated BCR-triggered phosphorylated ERK ex vivo, that are dependent on IL-4 and reversed by in vivo administration of neutralizing anti-IL-4 Ab. Thus, this study elucidates a novel mechanism for cross-talk between the IL-4 and BCRs that programs enhancement of subsequent BCR signaling.