A Hard(y) Look at B-1 Cell Development and Function

Abstract

A small population of B cells exists in lymphoid tissues and body cavities of mice that is distinct in development, phenotype, and function from the majority (B-2) B cell population. This population, originally termed "Ly-1" and now "B-1," has received renewed interest as an innate-like B cell population of fetal-derived hematopoiesis, responsible for natural Ab production and rapid immune responses. Molecular analyses have begun to define fetal and adult hematopoiesis, while cell-fate mapping studies have revealed complex developmental origins of B-1 cells. Together the studies provide a more detailed understanding of B-1 cell regulation and function. This review outlines studies that defined B-1 cells as natural Ab- and cytokine-producing B cells of fetal origin, with a focus on work conducted by R.R. Hardy, an early pioneer and codiscoverer of B-1 cells, whose seminal contributions enhanced our understanding of this enigmatic B cell population.

Figure 1. B-1 cells arise in waves from multiple precursors

Recent evidence suggests that multiple precursors give rise to waves of B-1 cells emerging mainly during embryonic development and at or shortly after birth. Earliest B-1 cell precursors have been found in the pre-HSC compartment of the embryonic yolk sac and are giving rise only to B-1 but not B-2 cells (36). Lineage-tracing studies indicated the presence of at least two distinct fetal HSC present in yolk sac and fetal liver, differing in expression of Flk2 (43). Flk2-expressing HSC have the highest B-1 cell reconstitution potential, but are transiently expressed only between E10.5 and about 2 weeks after birth. Adult HSC in the bone marrow have poor B-1 reconstitution potential. The distinct contributions of each of these heterogeneous precursor populations shape the peripheral B-1 cell pool and could shape also the functionality of this cell population.

Figure 2. Distribution and function of B-1 cells

(A) In steady state B-1 cells and B-1 cell-derived plasma cells in the spleen and bone marrow generate natural antibody, mostly IgM (81, 82). (B) B-1 cells make the majority B cell population in the peritoneal and pleural cavities. There they do not secrete but are activated by various innate signals, such as LPS (98, 109), IL-5, IL-10 (78) and Type I IFN (96) to rapidly migrate to secondary lymphoid tissues, such as lymph nodes and spleen, where they begin to secrete antibodies and/or cytokines (92, 96).