B Cell Receptor (BCR) Cross-Talk: CD40 Engagement Creates an Alternate Pathway for BCR Signaling That Activates IκB Kinase/IκBα/NF-κB without the Need for PI3K and Phospholipase Cγ

摘要: BCR signaling is propagated by a series of intermediaries and eventuates in NF-kappaB activation, among other outcomes. Interruption several mediators that constitute the signalosome, such as PI3K phospholipase Cgamma2, completely blocks for NF-kappaB. We show here this accepted, conventional paradigm is, fact, limited to naive B cells. CD40L treatment reprograms normal cells novel, alternate pathway created. Through triggering induces nuclear without need or Cgamma2. Induction via accompanied IkappaB kinase beta (IKKbeta) phosphorylation, IkappaBalpha degradation, inhibition IKKbeta blocked degradation. Several key events pathway, including early protein tyrosine were unimpeded generation which appears operate parallel, rather than competition, with classical signaling. These results demonstrate cross-talk between CD40 BCR, requirements are altered prior cell exposure CD40L. The bypasses multiple signalosome elements terminates activation.