IMMUNOGLOBULIN STRUCTURE & DIVERSITY--CHARACTERIZATION OF CELL MEMBRANE PROTEINS

点击翻译按钮获取中文摘要

I. Questions related to abnormal lymphocyte development are being approached in the plasmacytoma model developed by Dr. Michael Potter. One of the basic observations of plasmacytoma induction is that the BALB/c strain is highly susceptible, but others, including DBA/2, are resistant. We have examined the biological basis for DBA/2 resistance by a series of transfer experiments introducing either BALB/c or DBA/2 bone marrow into SCID mice followed by tumor induction protocols. Tumor induction has employed either classic pristane treatment or the use of a retroviral construct, J3Vl, supplying deregulated myc and raf oncogenes. These studies indicate that SCID mice reconstituted with BALB/c bone marrow and injected with J3Vl develop plasmacytomas and myeloid tumors. In contrast, DBA/2 reconstituted SCIDs develop only myeloid tumors indicating that the genetic difference between the two strains, in terms of plasmacytoma induction, resides in the DBA/2 B-cell and that resistance cannot be overcome by the introduction of a deregulated myc oncogene which seems to be critical for induction in BALB/c. II. The SCID mouse has additionally been used to study normal lymphocyte differentiation. We have initially reconstituted SCIDs with Peyer's patch cells as representatives of populations found in a specialized component of the mucosal immune system. Reconstituted SCID mice have been analyzed over a period of 6 months to establish both serum and tissue profiles. Reconstituted mice display a serum immunoglobulin profile similar to normal animals both qualitatively and quantitatively in spite of the fact that Peyer's patch B cells express only IgM and IgA. All lymphoid tissues including mucosal surfaces (gut, lungs), peripheral organs (spleen, lymph nodes) and the thymus are reconstituted. Normal anatomical structures such as spleen and lymph node germinal centers are readily visible in tissue sections. Thymic tissue reveals normal anatomical areas (cortex and medulla), but repopulation is by mature, single positive (CD4) or (CD8) T cells. Results of these studies have important implications for models of organ specific lymphocyte homing as well as concepts of cellular commitment during differentiation.