Given the importance of CD40 for class switching to occur in germinal centers (38), and the finding of decreased B cell CD40 expression in association with the MS risk allele rs4810485*T (39), we suggest that there may be impairment of normal class switching in CIS and MS mediated, in part, by a reduction in CD40–CD40L engagement on maturing B cells. Here, CD40LG is linked to in situ carcinoma.