A primary immunodeficiency patient was analysed whose serum
IgG and
IgE were extremely low but whose
IgM and
IgA levels were within the normal range or elevated. Southern blot analysis indicated no deletion of structural genes coding for C gamma, C epsilon, or C alpha. The majority of the patient's peripheral B cells expressed
IgM and
IgD on the surface yet
IgG-positive B cells were not detected, suggesting that the defect is in a switch-recombination process from
IgM to
IgG. The RFLP pattern detected with the S mu and S gamma
DNA regions revealed that there was no deletion or large mutation in the switch region
DNA. An in vitro
IgG production system with
pokeweed mitogen showed an abnormality at the transcriptional level and the defects were in both the patient's T and B cells. Addition of recombinant
IL-4 (rIL-4) to the normal B cells enhanced
IgG production but the patient's B cells did not respond to rIL-4, although the
IL-4 receptor was present at the normal level.
Messenger RNA and
IL-4 protein were not produced in the patient's T cells upon stimulation with
phorbol ester and
calcium ionophore, whereas
IL-2 was normally produced. The patient's lymphocytes showed a proliferative response to various
mitogens, including
phorbol ester. The transcripts of unrearranged C gamma region genes were not detected in the patient's lymphocytes, suggesting that the
chromatin structure of the S gamma region may not be open. These results suggest that the transcriptional defects at the S gamma region gene in B cells and at the
IL-4 gene in the T cells may be responsible for the present
IgG immunodeficiency. There might be a common transcriptional system operating in a certain step in the activation of both genes.