Altered lymphopoiesis and immunodeficiency in miR-142 null mice

Blood. 2015 Jun 11;125(24):3720-30. doi: 10.1182/blood-2014-10-603951. Epub 2015 Apr 30.


MicroRNAs (miRNAs) are a class of powerful posttranscriptional regulators implicated in the control of diverse biological processes, including regulation of hematopoiesis and the immune response. To define the biological functions of miR-142, which is preferentially and abundantly expressed in immune cells, we created a mouse line with a targeted deletion of this gene. Our analysis of miR-142(-/-) mice revealed a critical role for this miRNA in the development and homeostasis of lymphocytes. Marginal zone B cells expand in the knockout spleen, whereas the number of T and B1 B cells in the periphery is reduced. Abnormal development of hematopoietic lineages in miR-142(-/-) animals is accompanied by a profound immunodeficiency, manifested by hypoimmunoglobulinemia and failure to mount a productive immune response to soluble antigens and virus. miR-142(-/-) B cells express elevated levels of B-cell-activating factor (BAFF) receptor (BAFF-R) and as a result proliferate more robustly in response to BAFF stimulation. Lowering the BAFF-R gene dose in miR-142(-/-) mice rescues the B-cell expansion defect, suggesting that BAFF-R is a bona fide miR-142 target through which it controls B-cell homeostasis. Collectively, our results uncover miR-142 as an essential regulator of lymphopoiesis, and suggest that lesions in this miRNA gene may lead to primary immunodeficiency.

MeSH terms

  • Animals
  • B-Cell Activation Factor Receptor / genetics
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology*
  • Female
  • Gene Deletion*
  • Gene Expression Regulation
  • Gene Knockout Techniques
  • Immunity, Cellular
  • Immunity, Humoral
  • Immunologic Deficiency Syndromes / genetics*
  • Immunologic Deficiency Syndromes / immunology
  • Immunologic Deficiency Syndromes / pathology
  • Immunoproliferative Disorders / genetics*
  • Immunoproliferative Disorders / immunology
  • Immunoproliferative Disorders / pathology
  • Lymphopoiesis*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics*
  • MicroRNAs / immunology


  • B-Cell Activation Factor Receptor
  • MicroRNAs
  • Mirn142 microRNA, mouse
  • Tnfrsf13c protein, mouse