CD40 ligand triggers interleukin-6 mediated B cell differentiation.
Interleukin-6 (IL-6) is the major cytokine to date mediating antigen (Ag)- or mitogen-driven B cell differentiation. Recently, CD40 ligand (CD40L), with the co-stimulatory cytokines IL-4 and IL-10, has been shown to trigger immunoglobulin (Ig) secretion and class switching. In the present report, we have examined the role of IL-6 in mediating B cell differentiation and Ig secretion triggered with CD40L and/or these cytokines. Culture of splenic B cells with CD40L triggered (1) significant (5.4-fold) increases in IL-6 secretion; (2) differentiation, evidenced by sequential loss of B cell (CD20, CD21) and acquisition of plasma cell (CD38, PCA-1) surface antigens (Ags); and (3) Ig secretion. Interleukin-4 increased both IL-6 and IgG secretion stimulated by CD40L. Interleukin-10+ CD40L triggered 100-fold increments in IgG, IgA and IgM secretion, but IL-10 suppressed IL-6 secretion triggered with CD40L +/- IL-4. Exogenous IL-6 can further increase IgG secretion induced by CD40L + IL-10; moreover, the anti-IL-6 monoclonal antibody partially blocked IgG secretion triggered by CD40L +/- IL-4 or IL-10. Finally, IL-10 suppressed differentiation of B cells induced by CD40L. These studies suggest that CD40L augments Ig secretion in at least two mechanisms: by triggering IL-6 secretion and related differentiation, and by priming B cells for responsiveness to IL-10.
Urashima
M
M
Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Chauhan
D
D
Hatziyanni
M
M
Ogata
A
A
Hollenbaugh
D
D
Aruffo
A
A
Anderson
K C
KC
D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D023201:CD40 Ligand; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007136:Immunoglobulins / Q000502:physiology; D016753:Interleukin-10 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D010641:Phenotype; D012995:Solubility; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013268:Stimulation, Chemical
D007136:Immunoglobulins; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D016753:Interleukin-10; D023201:CD40 Ligand; D015847:Interleukin-4