Human Atypical B Cells. An Overview

Iñaki Sanz1

  • 1Division of Rheumatology, Department of Medicine, Lowance Center for Human Immunology, Emory University School of Medicine, Atlanta, Georgia, USA.

Immunological Reviews
|September 19, 2025
PubMed

Owing to their participation in diverse infections and autoimmune diseases, B cells lacking expression of CD27, having low CD21 levels or expressing markers such as CD11c or T-bet, have gained major prominence in the literature and are classified under the label of atypical B cells (AtB). Over time, different B cells (both of naïve and memory derivation) have been included in the AtB category on the basis of the expression of the above markers alone or in different combinations. In this review, we argue that the term AtB is obsolete as multiple studies indicate that these cells are a normal component of human immune responses. We review evidence indicating that the actual nature, derivation, and function of different categories of AtB cells depend on the context of the specific immune response under study and propose that the AtB label should be abandoned in favor of more precise classifications. Finally, we proposed that given the degree of functional diversity of these cells, specific functional studies rather than historical descriptions should be used to understand their actual role under different conditions.

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