A Room for Long-Lived Plasma Cell Contribution in Immune Cytopenias?

Immune cytopenias, such as autoimmune hemolytic anemia, immune thrombocytopenia, and Evans syndrome, are characterized by autoantibodies targeting various blood cells, initiating their destruction. Interactions between T cells, B cells, their ultimate maturational plasma cell descendants, dendritic cells, and macrophages result in antibody production, including the autoreactive ones. Autoimmune phenomena can be idiopathic or associated with various immune dysregulation conditions or malignancies. Interventions disrupting this complex network at different levels have been used to treat immune cytopenias with certain levels of success. Some cases are known to be refractory to many different therapeutic approaches, including the ones eliminating B cells. In some such cases, targeting plasma cells resulted in disease control. Among plasma cell compartments, unique long-lived plasma cells (LLPCs) residing primarily in the bone marrow, are specialized antibody-producing cells with an extended lifespan, capable of persistently secreting antibodies. LLPCs can evade conventional therapeutic strategies designed to target often-proliferating cells. Research focusing on the role of LLPCs in autoimmune phenomena including immune cytopenias has provided evidence for their role, characterized by the sustained production of autoantibodies. Frequent genetic mutations and progression to other immune dysregulation entities have been reported in a group of children with immune cytopenias. This might provide new insights focusing on the potential underlying genetic and epigenetic mechanisms leading to generation and maintenance of LLPCs in autoimmune disorders. We provide a brief review of LLPC biology and evidence for their role in immune cytopenias with potential future implications in this article.