Plasma Cell Ontogeny Defined by Quantitative Changes in Blimp-1 Expression

TLDR

Plasma cells are terminally differentiated B cells that require the transcriptional regulator Blimp‑1 for their development. Using a GFP reporter inserted into the Blimp‑1 locus, the authors showed that heterozygous mice label all antibody‑secreting cells, revealing that plasma cell maturation from plasmablasts to long‑lived bone‑marrow ASCs is driven by progressive quantitative increases in Blimp‑1 expression, with corresponding phenotypic and molecular heterogeneity.

Abstract

Plasma cells comprise a population of terminally differentiated B cells that are dependent on the transcriptional regulator B lymphocyte–induced maturation protein 1 (Blimp-1) for their development. We have introduced a gfp reporter into the Blimp-1 locus and shown that heterozygous mice express the green fluorescent protein in all antibody-secreting cells (ASCs) in vivo and in vitro. In vitro, these cells display considerable heterogeneity in surface phenotype, immunoglobulin secretion rate, and Blimp-1 expression levels. Importantly, analysis of in vivo ASCs induced by immunization reveals a developmental pathway in which increasing levels of Blimp-1 expression define developmental stages of plasma cell differentiation that have many phenotypic and molecular correlates. Thus, maturation from transient plasmablast to long-lived ASCs in bone marrow is predicated on quantitative increases in Blimp-1 expression.