Faculty Summaries
Richard R Hardy, PhD
Richard R Hardy, PhD
  • Director,
Office Phone: 215-728-2469
Lab Phone: 215-728-2463
Fax: 215-728-2412
Fetal and Adult B Lymphocyte Differentiation

B lymphocyte development in mouse, as in humans, takes place in the fetal liver before birth and shifts shortly thereafter to the bone marrow, where it continues throughout life. The generation of B cells is a highly ordered process, orchestrated by a number of transcription factors that regulate expression of a set of lymphoid and B lineage specific genes at well-defined developmental stages. During this process, immunoglobulin (Ig) heavy chain D-to-J rearrangements in pro-B cells precede V-to-DJ rearrangements that eventually yield functional heavy chain protein in pre-B cells. In pre-B cells, this Ig heavy chain protein associates with B lineage specific surrogate light chain components to form a pre-BCR. This signals events required for development to later stages where Ig light chain rearrangement takes place and is expressed. This then becomes associated with heavy chain, allowing a complete Ig molecule, the BCR, to be expressed on the surface of a newly formed B cell. The interests of my laboratory focus on three areas related to this process: 1) elucidating the stage(s) and molecular/cellular interactions taking place as B cell precursors become progressively restricted to the B lineage; 2) determining the role of Ig heavy chain VDJ structures in guiding B cell development; and 3) comparing fetal and adult B cell development, particularly as related to the preferential generation of autoreactive malignant-prone CD5+ ("B-1") B cells during embryogenesis. We are also investigating the peripheral maturation of B cells in spleen and recently, starting a project to mark B cells in the zebrafish.

Description of research projects
Selected Publications
  1. Amin RH, Cado D, Nolla H, Huang D, Shinton SA, Zhou Y, Hardy RR, Schlissel MS. Biallelic, ubiquitous transcription from the distal germline Ig kappa locus promoter during B cell development. Proc Natl Acad Sci U S A. 2009 Jan;106(2):522-7. PubMed
  2. Hardy RR. B lymphocyte development and biology. In: Paul WE, editor. Fundamental immunology. Philadelphia: Wolters Kluwer / Lippincott Williams & Wilkins; 2008. p. 237-69.
  3. Hardy RR, Kincade PW, Dorshkind K. The protean nature of cells in the B lymphocyte lineage. Immunity. 2007 Jun;26(6):703-14. PubMed
  4. Kitaura Y, Jang IK, Wang Y, Han YC, Inazu T, Cadera EJ, Schlissel M, Hardy RR, Gu H. Control of the B cell-intrinsic tolerance programs by ubiquitin ligases cbl and Cbl-b. Immunity. 2007 May;26(5):567-78. PubMed
  5. Hardy RR. B-1 B cells: development, selection, natural autoantibody and leukemia. Cur Opin Immunol. 2006;18:547-55. PubMed
  6. Rumfelt LL, Zhou Y, Rowley BM, Shinton SA, Hardy RR. Lineage specification and plasticity in CD19(-) early B cell precursors. J Exp Med. 2006 Mar;203(3):675-87. PubMed
  7. Wen L, Brill-Dashoff J, Shinton SA, Asano M, Hardy RR, Hayakawa K. Evidence of marginal-zone B cell-positive selection in spleen.[see comment]. Immunity. 2005 Sep;23(3):297-308. PubMed
  8. Maier H, Ostraat R, Gao H, Fields S, Shinton SA, Medina KL, Ikawa T, Murre C, Singh H, Hardy RR, Hagman J. Early B cell factor cooperates with Runx1 and mediates epigenetic changes associated with mb-1 transcription. Nat Immunol. 2004 Oct;5(10):1069-77. PubMed
  9. Hayakawa K, Asano M, Shinton SA, Gui M, Wen LJ, Dashoff J, Hardy RR. Positive selection of anti-Thy-1 autoreactive B-1 cells and natural serum autoantibody production independent from bone marrow B cell development. J Exp Med. 2003 Jan;197(1):87-99. PubMed
All publications