CD40LG and immune system disorder: While independent studies of fetal or early life B cells or B cells from patients with particular immunodeficiencies and single cell transcriptomic studies of splenic B cells support this concept (65, 75, 76, 78, 147, 150), it is still unresolved where in the human body SHM takes place outside of GC, and to what extent these early life lowly IgV mutated IgM+IgD+CD27+ B cells derive from either an antigen–independent primary diversification process or from TI immune responses.