Cellular basis of B cell clonal populations in old mice.

Previous studies from this laboratory have shown that >85% of old mice have stable B cell clonal populations detectable by Ig heavy chain complementary-determining region 3 mRNA size analysis and confirmed by sequence analysis. B cells from the same clone are frequently detected in several lymphoid compartments of the same mouse. We now report the phenotype of all ten stable B cell clonal populations detected in five 20-month-old C57BL/6 mice. These clonal B cells appear to develop in the periphery and nine of the ten B cell clonal populations expressed the CD5 cell surface marker. Stable B cell expansions may be dominated by cells at two stages of differentiation. Some B cell populations were detected with DNA as well as RNA and represent large clonal populations of B cells, detectable in several lymphoid compartments. These populations are found predominantly in B cell populations expressing CD45R/B220 and the mRNA coding for the membrane-bound form of the mu Ig heavy chain, which suggests a predominance of B lymphocytes in these populations. In other cases, smaller clonal populations were detected only in splenic RNA samples. These clonal populations were found predominantly among CD45R/B220- B cells and did not express the membrane-bound form of the micro Ig heavy chain. We offer the hypothesis that the B cell clonal populations present in old mice may be precursors of the two types of B cell neoplasms which are dominated by CD5+ B cells (B cell chronic lymphocytic leukemia) or plasma cells (multiple myeloma).

[1]  B. Mansa,et al.  A study of Russell bodies in human monoclonal plasma cells by means of immunofluorescence and electron microscopy. , 2009, Acta pathologica et microbiologica Scandinavica. Section A, Pathology.

[2]  P. Szabo,et al.  Increased VH 11 and VH Q52 gene use by splenic B cells in old mice associated with oligoclonal expansions of CD5+ B cells , 1998, Mechanisms of Ageing and Development.

[3]  P. Szabo,et al.  Effect of age on humoral immunity, selection of the B‐cell repertoire and B‐cell development , 1997, Immunological reviews.

[4]  P. Kourilsky,et al.  Clonal expansions of B lymphocytes in old mice. , 1997, Journal of immunology.

[5]  S. Bondada,et al.  CD5-Mediated Negative Regulation of Antigen Receptor-Induced Growth Signals in B-1 B Cells , 1996, Science.

[6]  S. Ikehara,et al.  Thymus transplantation, a critical factor for correction of autoimmune disease in aging MRL/+mice. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[7]  D. Fremont,et al.  T cell receptor (TCR) recognition of MHC class I variants: intermolecular second-site reversion provides evidence for peptide/MHC conformational variation , 1996, The Journal of experimental medicine.

[8]  K. Lam,et al.  B-1 cells: unique origins and functions. , 1996, Seminars in immunology.

[9]  A. Cumano,et al.  PCR-based analysis of the murine immunoglobulin heavy-chain repertoire. , 1995, Journal of immunological methods.

[10]  H. Wortis,et al.  B-cell activation by crosslinking of surface IgM or ligation of CD40 involves alternative signal pathways and results in different B-cell phenotypes. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[11]  P. Kourilsky,et al.  T-cell repertoire diversity and clonal expansions in normal and clinical samples. , 1995, Immunology today.

[12]  H. Wortis,et al.  Induction of CD5 on B and T cells is suppressed by cyclosporin A, FK-520 and rapamycin. , 1995, International immunology.

[13]  P. Youinou,et al.  CD5+ B cells and the immune system. , 1993, Immunology letters.

[14]  R. Hodes,et al.  CD45 expression by B cells. Expression of different CD45 isoforms by subpopulations of activated B cells. , 1992, Journal of immunology.

[15]  H. Wortis,et al.  Loss of CD23 Is a Consequence of B‐Cell Activation , 1992, Annals of the New York Academy of Sciences.

[16]  H. Wortis,et al.  Treatment of murine CD5- B cells with anti-Ig, but not LPS, induces surface CD5: two B-cell activation pathways. , 1991, International immunology.

[17]  K. Hayakawa Autoreactivity and CD5+ B cells. , 1990, Current opinion in immunology.

[18]  L. Herzenberg,et al.  Ly-1 B-cell clones similar to human chronic lymphocytic leukemias routinely develop in older normal mice and young autoimmune (New Zealand Black-related) animals. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[19]  D. Zharhary Age-related changes in the capability of the bone marrow to generate B cells. , 1988, Journal of immunology.

[20]  J. Teale,et al.  Comparison of the fetal and adult functional B cell repertoires by analysis of VH gene family expression , 1988, The Journal of experimental medicine.

[21]  P. Casali,et al.  Characterization of multireactive autoantibodies and identification of Leu-1+ B lymphocytes as cells making antibodies binding multiple self and exogenous molecules. , 1988, International reviews of immunology.

[22]  R. Hardy,et al.  Ly-1 B cells: functionally distinct lymphocytes that secrete IgM autoantibodies. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[23]  Y. Gozes,et al.  Selective decline in differentiating capacity of immunohemopoietic stem cells with aging , 1982, Mechanisms of Ageing and Development.

[24]  L. Lanier,et al.  Expression of Lyt-1 antigen on certain murine B cell lymphomas , 1981, The Journal of experimental medicine.

[25]  J. Rogers,et al.  Two mRNAs can be produced from a single immunoglobulin μ gene by alternative RNA processing pathways , 1980, Cell.

[26]  J. Rogers,et al.  Two mRNAs with different 3′ ends encode membrane-bound and secreted forms of immunoglobulin μ chain , 1980, Cell.

[27]  R. Good,et al.  STUDIES ON THYMUS FUNCTION , 1972, The Journal of experimental medicine.

[28]  A. L. Brown,et al.  Cytoplasmic and intranuclear electron-dense bodies in the myeloma cell. , 1966, Archives of pathology.

[29]  J. East,et al.  IMMUNOPATHOLOGY OF NEW ZEALAND BLACK (NZB) MICE , 1965, Transplantation.

[30]  H. Wortis,et al.  Activation of B-cells by sIgM cross-linking induces accumulation of CD5 mRNA. , 1995, Current topics in microbiology and immunology.

[31]  E. Kabat,et al.  Sequences of proteins of immunological interest , 1991 .

[32]  T. Kipps The CD5 B cell. , 1989, Advances in immunology.

[33]  J. H. Jandl Blood : textbook of hematology , 1987 .