IgM-IgG switch-over among antibody-forming cells in the mouse

DIFFERENTIATION of immunocytes from stem cells to antibody secreting B cells involves sequential expression of genes coding for heavy chain constant regions. This differentiation seems to be independent of thymus activity and antigen stimulation, for nude mice 1 and 15-week human foetuses 2 as well as germ-free mice 3 and piglets 4 have proportions of surface IgM, IgG or IgA bearing cells similar to those found in normal adults. It has therefore been suggested that the switch-over from IgM to IgG and IgA expression occurs before antigen contact which leads to differentiation from small B lymphocytes to plasma cells 5 . But during antibody production after antigenic stimulation a small proportion (1–3%) of mouse plaque-forming cells (PFC) secrete both IgM and IgG (refs 6, 7) and clones of cells derived from a single antigen-stimulated precursor secrete both IgM and IgG antibody 8 . These observations indicate that the IgM→IgG switch could be antigen driven. We have investigated the two alternatives by culturing individual PFC from mice immunised with sheep erythrocytes (SRBC) to study whether daughter PFC produce the same or a different Ig class. We have found that a part of IgM producing parental PFC can generate ‘in vitro’ IgG producing daughters, but this switch occurs only during the first 3 d after immunisation.