Activation of B1a Cells in Peritoneal Cavity by T Cell-Independent Antigen Expressed on Polymeric Micelle

Abstract

A polymeric micelle (Lactosome) composed of amphiphilic polydepsipeptide, poly(sarcosine)-block-poly(L-lactic acid), was reported as a T cell-independent antigen. We show here that Lactosome-responsive B cells are predominantly found in the peritoneal cavity (PerC). After immunization of mice with Lactosome, antibody-secreting cells (ASCs) are found only in spleen and bone marrow (BM), but not in PerC. The enzyme-linked immunospot assay shows that the dominant ASCs are plasmablasts in spleen. 5-Bromo-2'-deoxyuridine (BrdU) assay reveals that Lactosome-responsive peritoneal B1a cells proliferate by the stimulation of Lactosome and the majority of them stay there. These data indicate that the primary site for Lactosome to interact with B cells is in PerC, and some of activated B cells migrate into spleen or BM and differentiate into plasmablast there. As expected, when the B1a cells in PerC are collected from the Lactosome-immunized mice and are transplanted into recombination activating gene 2 (RAG2)(-/-) mice, the anti-Lactosome immunoglobulin M (IgM) production is observed in the recipient mice. It is therefore considered that the peritoneal B1a cells stimulated by Lactosome are the source of the sustained plasmablasts in spleen.