Intrathymic differentiation of natural antibody-producing plasma cells in human neonates

Hector Cordero, Rodney G. King, Pranay Dogra, Chloe Dufeu, Sarah B. See, Alexander M. Chong, Anne-Catrin Uhlemann, Siu-Hong Ho, David M. Kalfa, Emile A. Bacha, John F. Kearney and Emmanuel Zorn ()
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Hector Cordero: Columbia University Medical Center
Rodney G. King: University of Alabama at Birmingham
Pranay Dogra: Columbia University Medical Center
Chloe Dufeu: Columbia University Medical Center
Sarah B. See: Columbia University Medical Center
Alexander M. Chong: Columbia University Medical Center
Anne-Catrin Uhlemann: Columbia University Medical Center
Siu-Hong Ho: Columbia University Medical Center
David M. Kalfa: Columbia University Medical Center
Emile A. Bacha: Columbia University Medical Center
John F. Kearney: University of Alabama at Birmingham
Emmanuel Zorn: Columbia University Medical Center

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: Abstract The thymus is a central lymphoid organ primarily responsible for the development of T cells. A small proportion of B cells, however, also reside in the thymus to assist negative selection of self-reactive T cells. Here we show that the thymus of human neonates contains a consistent contingent of CD138+ plasma cells, producing all classes and subclasses of immunoglobulins with the exception of IgD. These antibody-secreting cells are part of a larger subset of B cells that share the expression of signature genes defining mouse B1 cells, yet lack the expression of complement receptors CD21 and CD35. Data from single-cell transcriptomic, clonal correspondence and in vitro differentiation assays support the notion of intrathymic CD138+ plasma cell differentiation, alongside other B cell subsets with distinctive molecular phenotypes. Lastly, neonatal thymic plasma cells also include clones reactive to commensal and 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.

Date: 2021
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DOI: 10.1038/s41467-021-26069-2

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