Intestinal nodular lymphoid hyperplasia in patients with common variable immunodeficiency: Local accumulation of B and CD8(+) lymphocytes

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Abstract
Common variable immunodeficiency (CVI) with hypogammaglobulinemia is often complicated by nodularlymphoid hyperplasia of the intestine. In this study the lymphoid constituents of intestinal nodular hyperplasia of five CVI patients were characterized with monoclonal antibodies. Few CD4(+) but abundant CD8(+) T lymphocytes were found around the follicles. The follicles were populated mainly by B cells expressing surface IgM. A few cells in the lamina propria expressed Leu7. No intracytoplasmic immunoglobulin-containing plasma cells were seen. Peyer's patches in gut biopsies from controls were also composed of follicles with B lymphocytes. A ring of T lymphocytes surrounded the follicles. CD4(+) helper cells largely outnumbered CD8(+) cells in this ring. Moreover, plasma cells were present in the lamina propria and the mixed cell zone covering the follicles. In peripheral blood of the patients, B cells were present in normal proportions but they could not be induced to produce IgGin vitro by T cell-dependent (pokeweed mitogen) or T cell-independent (Staphylococcus aureus Cowan I) mitogens. In two of the patients, IgM production could be inducedin vitro. Peripheral blood T cells were predominantly CD8(+) in three of the five patients, and in these same patients an increase in suppressor-cell activity of peripheral blood T cells on immunoglobulin production was observed. The data demonstrate a block in B-cell differentiation in the gut and in peripheral blood. Whether the local increase in CD8(+) cells in the nodular lymphoid hyperplasia is a primary event or is secondary to chronic immune stimulation and whether it contributes to local inhibition of B-cell differentiation remain to be investigated.