Nobue Takeda

Memory B cells without somatic hypermutation are generated from Bcl6-deficient B cells.

After immunization with T cell-dependent antigens, the high-affinity B cells selected in germinal centers differentiate into memory B cells or long-lived antibody-forming cells. However, a role for germinal centers in development of these B lineage cells is still controversial. We show here that Bcl6-deficient B cells, which cannot develop germinal centers, differentiated into IgM and IgG1 memory B cells in the spleen but barely differentiated into long-lived IgG1 antibody-forming cells in the bone marrow. Mutation in the V-heavy gene was null in these memory B cells. Therefore, Bcl6 and germinal center formation are essential for somatic hypermutation, and generation of memory B cells can occur independently of germinal center formation, somatic hypermutation, and Ig class switching.

Bcl6 Is a Transcriptional Repressor for the IL-18 Gene

Bcl6 functions as a sequence-specific transcriptional repressor, and Bcl6-deficient (Bcl6−/−) mice have been reported to display Th2-type inflammatory diseases in multiple organs. Since IL-18 is a potent stimulator of Th2 cells, we examined the expression of IL-18 mRNA in bone marrow-derived macrophages from Bcl6−/− mice after LPS stimulation. Here we show that the expression was strikingly up-regulated after stimulation. The expression was also up-regulated in RAW264 cells, a murine macrophage cell line, by transfection with the dominant negative type of Bcl6 gene. We identified a putative Bcl6-binding DNA sequence (IL-18BS) upstream of exon 1 of the murine IL-18 gene and three IL-18BSs in the promoter region of human IL-18 gene. Binding of Bcl6 in nuclear protein from resting RAW264 cells to murine IL-18BS was detected by gel retardation assay and chromatin immunoprecipitation assay. The binding activity was diminished gradually in RAW264 cells after LPS stimulation. However, the amount of Bcl6 protein in these cells was constant over the period examined, suggesting the functional modification of Bcl6 protein after stimulation. Furthermore, murine IL-18BS was required for Bcl6 to repress the expression of the luciferase reporter gene under control of the IL-18 promoter. Taken together, Bcl6 is a key regulator of IL-18 production by macrophages.

Intravenous immune globulin plus corticosteroids in refractory Kawasaki disease

Background:  The aim of the present study was to investigate the efficacy of i.v. immune globulin (IVIG) therapy combined with corticosteroids for additional treatment of acute Kawasaki disease (KD) unresponsive to initial IVIG treatment.

The clinical characteristics of Mycoplasma pneumoniae pneumonia in children younger than 6 years old

乳幼児のマイコプラズマ肺炎の臨床像を検討するため, 5歳以下43例を6歳以上40例と比較した。6歳以上に比べ5歳以下では咳噺の性状は湿性咳噺が90.0%を占め, 肺副雑音も83.7%に聴取し, 末梢血白血球数も10, 000/μL以上を示す症例がみられ成人市中肺炎診療ガイドラインに記載されている非定型肺炎の特徴とは異なる臨床像を認めた。また5歳以下の乳幼児では細気管支炎, 気管支喘息発作を合併する割合や, ウイルスや細菌の混合感染の割合が6歳以上より高率に認められ, 臨床像が成人と異なる要因と考えられた。年齢による微粒子凝集 (PA) 法による抗体価上昇の遅延は認めないが, 診断基準を満たす抗体価上昇に15日以上要した症例がみられた。以上より5歳以下のマイコプラズマ肺炎の臨床像は非典型的であり, 急性期に診断ができる感度のよい検査法もないため, 早期に有用な検査法の確立が望まれる。

Quantitative measurements of Hemophilus influenzae type b capsular polysaccharide antibodies in Japanese children.

Background: Hemophilus influenzae type b (Hib) infection has a high morbidity and mortality rate in children. The frequency of natural immunity against Hib in Japanese children is not known, and Hib vaccine has not yet been introduced in Japan.