The thymus is a central lymphoid organ responsible for the development of T cells. Here, we show that the thymus of human neonates also contains a consistent contingent of CD138+ plasma cells, producing all classes and subclasses of immunoglobulins with the exception of IgD. These antibody-secreting cells (ASC) are comprised within a larger subset of B cells lacking expression of the complement receptors CD21 and CD35 and sharing the expression of signature genes defining mouse B1 B cells. Single-cell transcriptomic analyses supported the intrathymic differentiation of CD138+ plasma cells alongside other B cell subsets with distinctive molecular phenotypes. Neonatal thymic plasma cells also included clones reactive to pathogenic bacteria that commonly infect children born with antibody deficiency. Thus, our findings point to the thymus as a source of innate humoral immunity in human neonates.

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