2.6.2 CD40
The proliferation and differentiation of B cells depend on the nuclear protein CD40, which is mediated by CD40L during development and binds to the surface receptors on B cells. In tumor tissues of patients with autoimmune disorders, upregulation of CD40/CD40L results in aberrant lymphangiogenesis and loss of lymphocyte function. In addition, autoimmune disorders might arise as a consequence of reduced CD40 activation. Uncertainty exists regarding the precise mechanisms by which CD40 influences the expression of other cell surface molecules. As multimeric CD40 ligands stimulate Daudi B cells and Chang Jiang et al68 discovered that cells with upregulated Fas expressed cd40l substantially more than other CD40 ligands, elevated Fas protein membrane (PM) content could be employed as a marker to identify this cell. The nuclear factor-B (NF-B), mitogen-activated kinase (MAPK) and phosphatidylinositol 3 kinase (PI3K) pathways that control Daudi B-cell differentiation and proliferation are affected by the accumulation of TNFR-related proteins after CD40 activation, which causes an increase of Fas in B cells. A non-classical CD40 transcription factor called FBXO11 is crucial for B-cell development. Reduced FBXO11 inhibits CD40 expression, mainly decreasing CD40L induced Fas expression without impairing TNF-α induced Fas expression. After knockout ELF1, CD40 induced Fas generation decreases, inhibiting the classical and non-classical MAPK pathway of CD40; ICAM-1 expression is suppressed, which is the target gene of CD40. High expression of m6A in cancer cells, m6A encoding protein WTAP and CD40 bind, can regulate the expression level of m6A, affect cell proliferation. Bispecific serine/threonine phosphatase DUSP10 In the CD40 negative regulator screen, DUSP10 is the primary B-cell negative feedback regulator of the CD40 / MAPK pathway.