CD40LG and in situ carcinoma: The pathological significance of B1 cells in MS is reinforced by data showing that elevated levels of peripheral B1a cells and IgM OCB (presumably from CD5+ B cells) are highly predictive of poor prognosis and transition from “clinically isolated syndrome” to RRMS (CIS: a first, single episode of MS relapse-like symptoms that often progress to RRMS) [33,193,197].