However, deficiencies in C1q, C1r/C1s and C4, in addition to increasing the susceptibility to infection, are strongly associated with antinuclear autoimmunity individually.29,51 C1q protective role against autoimmunity revolves around its function in the clearance of apoptotic cellular debris and suppression of immune responses.14,15,17–20,52 For C4, its role in maintaining B cell tolerance was demonstrated using C4−/− mice; these mice displayed increased germinal center numbers and reactions with anti-nucleolus autoreactive B cells.53 This evidence concerns the gene C4A and Autoimmunity.