Antibodies against bromelain-treated erythrocytes occurring in normal mice are germline gene-encoded IgM natural autoantibodies that are secreted by CD5+ B cells, and react primarily with phosphatidylcholine (PTC), but may crossreact with cardiolipin (aCL). Some of the IgM antiphospholipid antibodies (aPL) present in patients with the recently described primary antiphospholipid syndrome (PAPS) also react with PTC and could thus be natural autoantibodies akin to those found in mice. Patients with PAPS (n = 20) were found to have increased total B cells, as well as CD5 + B cells, in their peripheral blood, but normal total lymphocytes, as well as CD4 and CD8 T lymphocytes, compared to normal controls. The 6 PAPS patients with increased CD5+ B cells were found to have increased levels of IgM aPL, including aPTC. In them we also found a correlation between the number of CD5+ B cells and the levels of IgM aCL. Our findings suggest that within the family of aPLs present in patients with PAPS there may be some that could be IgM natural autoantibodies secreted by CD5+ B cells.