Disruption of IGF1R signalling in human RA and experimental mouse model results in involution of the FOXO pathway, which prolongs communication between macrophages and B cells and, under the condition of insufficient T cell feedback, permits the production of IgM that targets the canonical auto-antigens dsDNA, Fc-portion of IgG, and cyclic citrullinated peptides with well-documented pathogenic potential. This evidence concerns the gene CD40LG and rheumatoid arthritis.