Blimp-1–dependent and –independent natural antibody production by B-1 and B-1–derived plasma cells

Abstract

The transcriptional regulator of B cell differentiation, Blimp-1, regulates antibody production by plasma cells after antigen stimulation. Savage et al. demonstrate that spontaneous “natural” IgM and IgG3 production is provided by a heterogeneous set of B-1–derived plasma cells and by B-1 cells; the latter neither express nor require Blimp-1 for maximal antibody production.

Abstract

Natural antibodies contribute to tissue homeostasis and protect against infections. They are secreted constitutively without external antigenic stimulation. The differentiation state and regulatory pathways that enable continuous natural antibody production by B-1 cells, the main cellular source in mice, remain incompletely understood. Here we demonstrate that natural IgM-secreting B-1 cells in the spleen and bone marrow are heterogeneous, consisting of (a) terminally differentiated B-1–derived plasma cells expressing the transcriptional regulator of differentiation, Blimp-1, (b) Blimp-1 ⁺, and (c) Blimp-1 ^neg phenotypic B-1 cells. Blimp-1 ^neg IgM-secreting B-1 cells are not simply intermediates of cellular differentiation. Instead, they secrete similar amounts of IgM in wild-type and Blimp-1–deficient (PRDM-1 ^ΔEx1A) mice. Blimp-1 ^neg B-1 cells are also a major source of IgG3. Consequently, deletion of Blimp-1 changes neither serum IgG3 levels nor the amount of IgG3 secreted per cell. Thus, the pool of natural antibody-secreting B-1 cells is heterogeneous and contains a distinct subset of cells that do not use Blimp-1 for initiation or maximal antibody secretion.