B cell differentiation. II. Isotype potential of a single B cell.
Clonal, functionally responsive B cells are important tools for analyzing B cell activation and differentiation. Previously, we developed a method to immortalize murine B lymphoblast cells using an oncogene-carrying retroviral vector. The immortalized B cells express a cell surface phenotype similar to that of normal splenic B cells. These cells were shown to respond to B cell polyclonal mitogens and IL-4. More significantly, these cells could form conjugates with TH2 cells in the presence of a T cell superantigen. The T-B interaction promoted by the T cell superantigen resulted in B cell differentiation as demonstrated by IgM secretion and switching to IgG1 production. In this report, we analyze Ig isotype potential using two retrovirus-immortalized B cell clones. The clonality of both B cell clones was confirmed by Southern blot analysis using JH probes. It was found that anti-CD3-activated TH1 and TH2 cells promoted clonal B cells to differentiate into IgM-secreting cells. More significantly, activated TH1 cells promoted clonal B cells to switch to IgG2a production, whereas activated TH2 cells promoted clonal B cells to switch to IgG1 production. Thus, depending on which type of T helper cell a given B cell interacts with, a single B cell has the potential to switch to more than one Ig isotype. Addition of rIL-4 and anti-IFN-gamma to cultures containing TH1 and B cells resulted in IgG1 production (in addition to IgG2a production). Similarly, addition of IFN-gamma and anti-IL-4 to cultures containing TH2 and B cells resulted in IgG2a production (in addition to IgG1 production). Therefore, interaction of B cells with a given type of T helper cells could commit the B cells to a given Ig isotype. However, the presence of exogenous cytokines could divert B cells to switch to other Ig isotypes.
Lin
M S
MS
Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
Chen
Y W
YW
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology*; D017252:CD3 Complex / Q000276:immunology; D002454:Cell Differentiation; D002999:Clone Cells; D007074:Immunoglobulin G / Q000096:biosynthesis; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*
D000954:Antigens, Surface; D017252:CD3 Complex; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D015847:Interleukin-4; D007371:Interferon-gamma