INABILITY TO PRODUCE IL-6 IS A FUNCTIONAL FEATURE OF HUMAN GERMINAL CENTER B-LYMPHOCYTES

In response to Ag encounter, B lymphocytes undergo a complex maturatio n process yielding phenotypically distinct subpopulations that are loc ated in highly organized compartments of secondary lymphoid organs, Th is study describes the patterns of cytokine secretion of naive, memory , and germinal center (GC) human tonsillar B lymphocytes, activated ei ther through CD40 or B cell receptor or with Staphylococcus aureus Cow an I particles. The three B cell subpopulations produced comparable le vels of IL-10 and TNF-alpha, regardless of the stimulation pathway. In terestingly, activated GC B lymphocytes fail to express IL-6, as deter mined both at mRNA and at protein levels, whereas both naive and memor y B cells can be induced to secrete IL-6. Likewise, naive B lymphocyte s undergoing dual ligation of CD40 and B cell receptor fail to express IL-6, since they acquire a GC-like phenotype, IL-6 receptors are up-r egulated on both ex vivo-purified CC B lymphocytes and in vitro genera ted GC-like B cells, following CD40 activation, Consistent with this, addition of exogenous IL-6 sustains growth of CD40-stimulated GC B lym phocytes. Taken together, these results demonstrate that loss of IL-6 secretion is a functional characteristic of human GC B lymphocytes, Th e swap from an autocrine to a paracrine IL-6 response may permit a bet ter control of B cell growth and differentiation during the germinal c enter reaction.