B cells in primary antiphospholipid syndrome: Review and remaining challenges

It is now widely accepted that antiphospholipid antibodies (aPL) have direct pathogenic effects and that B cells, notably through aPL production, play a key role in the development of antiphospholipid syndrome (APS). Recent findings strengthened the implication of B cells with the description of specific B cell phenotype abnormalities and inborn errors of immunity involving B cell signaling in APS patients. In addition, it has been shown in preclinical models that cross-reactivity between APS autoantigens and mimotopes expressed by human gut commensals can lead to B cell tolerance breakdown and are sufficient for APS development. However, B cell targeting therapies are surprisingly not as effective as expected in APS compared to other autoimmune diseases. Elucidation of the B cell tolerance breakdown mechanisms in APS patients may help to develop and guide the use of novel therapeutic agents that target B cells or specific immune pathway. •The hypercoagulable state in antiphospholipid syndrome (APS) is related to pathogenic antiphospholipid antibodies (aPL).•B cells, notably through aPL production, have a central role in the pathogenesis of APS.•aPL development may result from mono/polygenic inborn errors of immunity and specific interactions with commensal hosts.•Paradoxically, B cell targeting therapies are disappointing in APS as compared to experiences in other autoimmune diseases.