Whether failure to induce CTLA-4 expression on CD4+ Tfh1 cells in MS-OCR patients is the result of a less tolerant immune system as part of the autoimmune disease or a direct result of missing B cells in the germinal response which may normally be responsible for the induction of CTLA-4 on CD4+ Tfh1 cells as part of a negative feedback loop remains to be established. The gene discussed is CD4; the disease is autoimmune disease.