B cell differentiation and isotype switching is related to division cycle number

• Published in: The Journal of experimental medicine Vol. 184; no. 1; pp. 277 - 281
• Main Authors: Hodgkin, P D, Lee, J H, Lyons, A B
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 01-07-1996
• Subjects: Animals; Antigens, Differentiation, B-Lymphocyte - analysis; B-Lymphocytes - cytology; B-Lymphocytes - immunology; Cell Cycle; Cell Differentiation; Flow Cytometry; Gene Rearrangement, B-Lymphocyte; Immunoglobulin G - metabolism; Immunoglobulin Isotypes - genetics; Lymphocyte Activation; Membrane Glycoproteins - metabolism; Mice; Mice, Inbred CBA; Proteoglycans - metabolism; Syndecans
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.184.1.277

The mature, resting immunoglobulin (Ig) M, IgD+ B lymphocyte can be induced by T cells to proliferate, switch isotype, and differentiate into Ig-secreting or memory cells. Furthermore, B cell activation results in the de novo expression or loss of a number of cell surface molecules that function in cell recirculation or further interaction with T cells. Here, a novel fluorescent technique reveals that T-dependent B cell activation induces cell surface changes that correlate with division cycle number. Furthermore, striking stepwise changes are often centered on a single round of cell division. Particularly marked was the consistent increase in IgG1+ B cells after the second division cycle, from an initial level of < 3% IgG1+ to a plateau of approximately 40% after six cell divisions. The relationship between the percentage of IgG1+ B cells and division number was independent of time after stimulation, indicating a requirement for cell division in isotype switching. IgD expression became negative after four divisions, and a number of changes centered on the sixth division, including the loss of IgM, CD23, and B220. The techniques used here should prove useful for tracking other differentiation pathways and for future analysis of the molecular events associated with stepwise differentiation at the single cell level.