Analysis of B cell dysfunction in patients with common variable immunodeficiency by using recombinant interleukin 2.

Recombinant interleukin 2 (RIL2) induces proliferation and differentiation of the Staphylococcus aureus Cowan I (SAC)-activated normal B cells to immunoglobulin (Ig) producting cells. We applied this finding to an analysis of heterogeneity in the differentiation states of B cells in patients with common variable immunodeficiency (CVI). B cells from 5 of 7 patients with CVI were tested for their ability to proliferate under the stimulation of SAC, or SAC and RIL2, and for their differentiation to Ig producing cells in the presence of SAC plus RIL2. The results suggest that the differentiation status of B cells in CVI could be divided into four states based on their responses to SAC and RIL2. In the first state, no B cell proliferation or differentiation was demonstrated in our assays. B cells in the second state showed normal proliferative responses to SAC, but not to SAC plus RIL2, and no differentiation to Ig-secreting cells. The third state showed normal proliferation in response to SAC and SAC plus RIL2, but no differentiation to Ig-secreting cells. The fourth state had a normal proliferation response to SAC and SAC plus RIL2, and normal secretions of IgG and IgM in response to SAC and RIL2. These results show that some B cells in CVI have defects in response to RIL2, and at least in terms of defect of B cells, CVI is heterogeneous.