The present study analyzed peripheral blood B cell populations separated by
IgD and CD27 expression in six males with
X-linked hyper-IgM syndrome (XHIM). Costimulation of mononuclear cells from most of the patients induced no to low levels of class switching from
IgM to
IgG and
IgA with Staphylococcus aureus Cowan strain (SAC) plus
IL-2 or anti-CD40 mAb (anti-CD40) plus
IL-10. Measurable levels of
IgE were secreted in some of the patients after stimulation with anti-CD40 plus
IL-4. Costimulation with SAC plus
IL-2 plus anti-CD40 plus
IL-10 yielded secretion of significant levels of
IgG in addition to
IgM, but not
IgA. The most striking finding was that peripheral blood B cells from all of the six patients were composed of only IgD+ CD27(-) and IgD+ CD27(+) B cells;
IgD- CD27(+) memory B cells were greatly decreased. IgD+ CD27(+) B cells from an XHIM patient produced
IgM predominantly. Our data indicate that the low response of
IgG production in XHIM patients is due to reduced numbers of
IgD- CD27(+) memory B cells. However, the
IgG production can be induced by stimulation of
immunoglobulin receptors and CD40 in cooperation with such
cytokines as
IL-2 and
IL-10 in vitro.