Human low molecular weight B cell growth factor induces surface IgM+/A- B cells to express and secrete IgA.
The regulation of Ig class expression has been a controversial area of research. It is well established that T cells, and/or their products, influence which Ig isotype is produced during an immune response. In this study the regulation of Ig secretion of activated human IgM+/A- B cells was examined. Human T cell supernatants induced PWM-activated IgM+/A- B cells to switch to IgA secretion. Purification of the lymphokine mediating this effect involved hydroxylapatite, ion exchange, and gel filtration chromatography. The purified lymphokine could induce switch of IgM+/A- B cells, and it was also capable of inducing proliferation of Staphylococcus aureus Cowan 1 strain (SAC)-activated IgM+/A- B cells. SDS-PAGE and isoelectric focusing indicated the protein mediating this activity had a molecular mass of approximately 14 kDa and a pI of 6.8. These results suggested that the observed activity might be due to low m.w. B cell growth factor (LMW-BCGF), a lymphokine which is capable of inducing proliferation of SAC-activated B cells and has a molecular weight and pI value in the range of the purified protein. Indeed, rLMW-BCGF was able to switch IgM+/A- B-cells to IgA expression and secretion as well as induce the proliferation of SAC-activated IgM+/A- B cells. These results demonstrate that LMW-BCGF is capable of inducing PWM-activated IgM+/A- B-cells to switch to IgA possibly by providing a proliferation signal which induces clonal expansion of IgM+/A- B cells, the progeny of which express a range of isotypes including IgA. This study also demonstrates that lymphokine induced isotype switching involves an intermediate stage of B cell development where human B cells coexpress IgM and a downstream isotype on their surface.
Bertolini
J N
JN
Department of Pathology and Immunology, Monash Univesity Medical School, Alfred Hospital, Prahran, Victoria, Australia.
Bertolini
J
J
Thean
E
E
Benson
E M
EM
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D005803:Genes, Immunoglobulin; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis*; D007071:Immunoglobulin A, Secretory / Q000378:metabolism*; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D007132:Immunoglobulin Isotypes / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis*; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D007378:Interleukins / Q000494:pharmacology; D008213:Lymphocyte Activation; D008970:Molecular Weight; D011817:Rabbits; D011947:Receptors, Antigen, B-Cell / Q000032:analysis*; D013601:T-Lymphocytes / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D007070:Immunoglobulin A; D007071:Immunoglobulin A, Secretory; D007127:Immunoglobulin Constant Regions; D007132:Immunoglobulin Isotypes; D007075:Immunoglobulin M; D007378:Interleukins; D011947:Receptors, Antigen, B-Cell; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D007371:Interferon-gamma