At least three B cell subsets, B-1a, B-1b and B-2, or conventional B cells are present in the mouse periphery. Here we demonstrate that B-1 cells spontaneously proliferate in stationary cultures of normal adherent mouse peritoneal cells. B-1 cells were characterized by morphology, immunohistochemistry and flow cytometry. IgM was detected in the supernatants of these cultures. We demonstrated that the major cell population analyzed expresses the B-1b phenotype. When these cells were transferred to a new culture, a large proportion of them adhere to the plastic surface, and spread as bipolar cells endowed with the capacity to phagocytose via Fc and mannose receptors. Flow cytometry analysis of these adherent cells demonstrated that the great majority of them share both B-220 and Mac-1 antigens. Nevertheless, 45% of them were exclusively Mac-1(+). Finally, when they were labeled in vitro with [(3)H]thymidine and transferred to the peritoneal cavity of naive mice, they migrate to a non-specific inflammatory focus induced by a foreign-body implant. These data demonstrate that B-1 cells, mainly B-1b cells, not only proliferate and differentiate into a mononuclear phagocyte in vitro, but also that they exit the peritoneal cavity and migrate to a non-specific inflammatory milieu.
Co-ordinated expression of lymphoid and myeloid specific transcription factors during B-1b cell differentiation into mononuclear phagocytes in vitro
IntroductionThe distinct origins, properties and fates of myeloid and lymphoid cell lineages have been clearly established since the beginning of the 1970s.1,2 Pluripotent haematopoietic stem cells give rise to all mature blood cell types through a stepwise process of binary decisions, in which multipotent progenitors undergo lineage commitment, branching into an intermediate progenitor that develops along a single pathway.1,2 It is hypothesized that the first decision of haematopoietic stem cells determines their fate as either lymphoid or myeloid cells. The lineage commitment is thought to be an irreversible process, restricting the developmental fate of a progenitor cell to a single lineage by mutual antagonism of lineagespecific transcription factors.2 Nevertheless, there is evidence that, in CD5 + -derived lymphomas, pre-B cells acquire macrophage characteristics in vitro and 'monocytoid B lymphocytes' have also been found to be associated with human diseases such as AIDS, chronic lymphocytic leukaemia, Sjögren's syndrome and Hodgkin's disease. [3][4][5][6] This bipotential phenotype could be considered a consequence of inadequate gene expression related to malignancy of these cells.However, the discovery of B-1 cells by Hayakawa et al. 7 disproved this hypothesis. B-1 cells were originally identified in the murine peritoneum, as a B-lymphocyte subset that differs from conventional B-2 cells or B lymphocytes in terms of phenotypic, functional and developmental characteristics. These differences have been extensively reviewed. [8][9][10][11][12] A striking distinction between these cells is that the immunoglobulin repertoire of B-1 cells is less diverse compared with that of B-2 cells. B-1 cells tend to express B-cell receptors with particular specificities; for example, approximately 10-15% of peritoneal B-1 cells are specific for the membrane phospholipid phosphatidylcholine. This specificity is commonly produced by the heavy chain variable (V) genes VH11 and VH12, which are expressed at high levels in B-1 cells, but not in B-2 cells.
SUMMARYAs demonstrated previously in our laboratory, B-1 cells migrate from the peritoneal cavity of mice and home to a distant site of inflammation to become macrophage-like cells. However, the influence that these cells might have on the kinetics and fate of the inflammatory process is not known. Considering that macrophages are pivotal in the inflammatory reaction, we decided to investigate the possible influence B-1 cells could have on macrophage activities in vitro. Our results show that peritoneal macrophages from Xid mice, a mouse strain deprived of B-1 cells, have higher phagocytic indexes for zymozan particles when compared with macrophages from wild-type mice. Moreover, macrophages from wild-type mice have a lower ability to release nitric oxide and hydrogen peroxide when compared with macrophages from Xid mice. Experiments using cocultures of B-1 cells and macrophages from Xid mice in transwell plates demonstrated that B-1 cells down-regulate macrophage activities. These observations also indicate that this phenomenon is not due to a physical interaction between these two cell populations. As B-1 cells are one of the main sources of interleukin (IL)-10, we demonstrate in this study that adherent peritoneal cells from Xid mice produce significantly less amounts of this cytokine in culture when compared with IL-10 production by cells from wild-type mice. When B-1 cells from IL-10 knock-out mice and macrophages from wild-type mice were cocultured in transwell plates, the phagocytic index of macrophages was not altered demonstrating that B-1 cells can influence the effector functions of macrophages in vitro via IL-10 secretion.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.