NFkB alternative pathway is activated in IgE class switching

IgE class switch recombination is regulated by CaMKII via NF-κB alternative pathway

IgE class switch recombination (CSR) is under the tight control to maintain the low concentration of serum IgE. IL-4 and CD40 signal induces IgE CSR. NF-κB classical pathway and STAT6 was indicated in this pathway. In this study, we prepared a M12 cell line expressing TRAF3 in an inducible manner. This cell line showed impaired signal transduction of NF-κB alternative pathway and diminished exp...

IgE Class Switching Measles Virus Infection Synergizes with IL-4

Sequential class switching is required for the generation of high affinity IgE antibodies

IgE antibodies with high affinity for their antigens can be stably cross-linked at low concentrations by trace amounts of antigen, whereas IgE antibodies with low affinity bind their antigens weakly. In this study, we find that there are two distinct pathways to generate high and low affinity IgE. High affinity IgE is generated through sequential class switching (μ→γ→ε) in which an intermediary...

A critical role for the NFkB pathway in multiple myeloma

NFkB transcription factors play a key role in the survival and proliferation of many kinds of B-cell tumors, including multiple myeloma (MM). It was shown that NFkB activation in MM tumors results mainly from extrinsic signaling by APRIL and BAFF ligands that stimulate receptors on normal plasma cells as well as on pre-malignant monoclonal gammopathy of undetermined significance (MGUS) and MM t...

Intrinsic transcriptional heterogeneity in B cells controls early class switching to IgE

Noncoding transcripts originating upstream of the immunoglobulin constant region (I transcripts) are required to direct activation-induced deaminase to initiate class switching in B cells. Differential regulation of Iε and Iγ1 transcription in response to interleukin 4 (IL-4), hence class switching to IgE and IgG1, is not fully understood. In this study, we combine novel mouse reporters and sin...