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<p>The RNA binding protein Sam68 (Src associated during mitosis of 68&#xa0;kDa) has recently been shown to be involved in DNA double strand break repair. In the course of development and immune response, B cells undergo physiological double strand breaks during V(D)J recombination and class switch recombination. Therefore, envisaging a crucial role of Sam68 in B cell development and function, we analyzed Sam68 complete knockout (KO) mice. Despite normal B cell development, these animals exhibit impaired germinal centre (GC) reactions and antibody responses. Using a competitive bone marrow chimera model, as well as adoptive B cell transfer model, we could demonstrate that Sam68 deficient B cells are less competent to participate in GC than WT B cells. This reduced competence is mainly attributed to impaired B cell-intrinsic CD40 signaling as Sam68 KO B cells are less responsive to CD40 stimulation in vitro. Sam68 deficient B cells up-regulate the expression of microRNA miR29a and b which in turn repress the expression of Tumor necrosis factor receptor-associated factor 4 (<i>Traf4</i>) gene, a downstream effector molecule of CD40 pathway. Thus, Sam68 mediated Traf4 regulation through miR29 plays an important role in CD40 signaling in B cells, hence in GC response.</p>

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RNA binding protein Sam68 promotes germinal center reaction and IgG response through regulation of miR29

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月7日

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  • Moumita Datta,
  • Valerio Renna,
  • Manish Kumar,
  • Palash Chandra Maity,
  • Hassan Jumaa

摘要

The RNA binding protein Sam68 (Src associated during mitosis of 68 kDa) has recently been shown to be involved in DNA double strand break repair. In the course of development and immune response, B cells undergo physiological double strand breaks during V(D)J recombination and class switch recombination. Therefore, envisaging a crucial role of Sam68 in B cell development and function, we analyzed Sam68 complete knockout (KO) mice. Despite normal B cell development, these animals exhibit impaired germinal centre (GC) reactions and antibody responses. Using a competitive bone marrow chimera model, as well as adoptive B cell transfer model, we could demonstrate that Sam68 deficient B cells are less competent to participate in GC than WT B cells. This reduced competence is mainly attributed to impaired B cell-intrinsic CD40 signaling as Sam68 KO B cells are less responsive to CD40 stimulation in vitro. Sam68 deficient B cells up-regulate the expression of microRNA miR29a and b which in turn repress the expression of Tumor necrosis factor receptor-associated factor 4 (Traf4) gene, a downstream effector molecule of CD40 pathway. Thus, Sam68 mediated Traf4 regulation through miR29 plays an important role in CD40 signaling in B cells, hence in GC response.