Lymphoblastoid cell lines do not recapitulate physiological circulating B cell subtypes

Abstract

Lymphoblastoid cell lines (LCLs) are immortalised peripheral B lymphocytes, transformed via infection with Epstein Barr virus (EBV). The use of LCLs to study B cell function remains controversial and core markers to define physiological B cell populations are not consistent between studies of physiological B cells and LCLs. A consensus on the nature of these commonly used cell lines has not been reached. Recently, a core set of markers to subtype peripheral B cells was proposed, addressing the lack of agreed markers for B cell characterisation. In this present study, the consensus panel was applied to describe the B cell subtypes in LCLs. We found that LCLs were generally not physiologically representative of B cells, with most cells harbouring marker combinations absent on peripheral B cells. Some B cell subtyping markers were fundamentally altered during EBV transformation to LCLs (e.g. CD19, CD21). Notably, most LCLs secreted IgG but the associated marker combinations were predominantly only present in vitro following EBV transformation. This study therefore informs interpretation of past investigations, and planning of future studies using LCLs, as these cells are unlikely to behave like their pre-transformed B cell subtype.