Clonal dissection of the human memory B‐cell repertoire following infection and vaccination

The analysis of the human memory B‐cell repertoire is of both fundamental and practical significance. We developed a simple method for the selective activation of memory B cells in total fresh or frozen PBMC using a combination of R848 and IL‐2. In these conditions, 30–40% of memory B cells generated clones producing on average 200 ng IgG in 10 days. This method was used to measure the frequency of antigen‐specific memory B cells as well as the fine specificity, cross‐reactivity and neutralizing activity of the secreted antibodies. Following influenza vaccination, specific B cells expanded dramatically, reaching up to 50% of total clonable memory B cells on day 14. Specific B‐cell expansions were detected also in individuals that did not show a significant serological response. Dynamic changes and persistence of B cells specific for a variety of pathogens were documented in serial PBMC samples collected over almost two decades. These results reveal novel aspects of memory B‐cell kinetics and provide a powerful tool to monitor immune responses following infection and vaccination.

[1]  C. Picard,et al.  Somatic diversification in the absence of antigen-driven responses is the hallmark of the IgM+IgD+CD27+ B cell repertoire in infants , 2008, The Journal of experimental medicine.

[2]  A. Cerutti The regulation of IgA class switching , 2008, Nature Reviews Immunology.

[3]  Patrick C. Wilson,et al.  Rapid cloning of high-affinity human monoclonal antibodies against influenza virus , 2008, Nature.

[4]  Jacques-Olivier Pers,et al.  The human spleen is a major reservoir for long-lived vaccinia virus-specific memory B cells. , 2008, Blood.

[5]  M. Ait-goughoulte,et al.  Antibody-Dependent Enhancement of Hepatitis C Virus Infection , 2007, Journal of Virology.

[6]  Nichole E Carlson,et al.  Duration of humoral immunity to common viral and vaccine antigens. , 2007, The New England journal of medicine.

[7]  D. Burton,et al.  Fc receptor but not complement binding is important in antibody protection against HIV , 2007, Nature.

[8]  M. Nussenzweig,et al.  Autoreactivity in human IgG+ memory B cells. , 2007, Immunity.

[9]  M. Slifka,et al.  Quantitation of rare memory B cell populations by two independent and complementary approaches. , 2006, Journal of immunological methods.

[10]  J. Battiste,et al.  Oligodeoxynucleotides Differentially Modulate Activation of TLR7 and TLR8 by Imidazoquinolines , 2006, The Journal of Immunology.

[11]  A. Lanzavecchia,et al.  ABCB1 transporter discriminates human resting naive B cells from cycling transitional and memory B cells , 2005, European journal of immunology.

[12]  L. Brown,et al.  Enumeration and characterization of virus-specific B cells by multicolor flow cytometry. , 2005, Journal of immunological methods.

[13]  C. Berek,et al.  Generation of migratory antigen-specific plasma blasts and mobilization of resident plasma cells in a secondary immune response. , 2005, Blood.

[14]  Andreas Radbruch,et al.  Maintenance of serum antibody levels. , 2005, Annual review of immunology.

[15]  L. McHeyzer-Williams,et al.  Antigen-specific memory B cell development. , 2005, Annual review of immunology.

[16]  L. Staudt,et al.  Human blood IgM "memory" B cells are circulating splenic marginal zone B cells harboring a prediversified immunoglobulin repertoire. , 2004, Blood.

[17]  B. Murphy,et al.  An efficient method to make human monoclonal antibodies from memory B cells: potent neutralization of SARS coronavirus , 2004, Nature Medicine.

[18]  R. Ahmed,et al.  Tracking human antigen-specific memory B cells: a sensitive and generalized ELISPOT system. , 2004, Journal of immunological methods.

[19]  Luis Villarreal,et al.  Cutting Edge: Long-Term B Cell Memory in Humans after Smallpox Vaccination 1 , 2003, The Journal of Immunology.

[20]  Uwe Schauer,et al.  IgG subclass concentrations in certified reference material 470 and reference values for children and adults determined with the binding site reagents. , 2003, Clinical chemistry.

[21]  A. Lanzavecchia,et al.  A role for Toll-like receptors in acquired immunity: up-regulation of TLR9 by BCR triggering in naive B cells and constitutive expression in memory B cells. , 2003, Blood.

[22]  Xi Jiang,et al.  Human susceptibility and resistance to Norwalk virus infection , 2003, Nature Medicine.

[23]  Thomas Boehm,et al.  Human Immunoglobulin M Memory B Cells Controlling Streptococcus pneumoniae Infections Are Generated in the Spleen , 2003, The Journal of experimental medicine.

[24]  F. Sallusto,et al.  Cytokine-driven proliferation and differentiation of human naïve, central memory and effector memory CD4+ T cells. , 2003, Pathologie-biologie.

[25]  S. Halstead,et al.  Neutralization and antibody-dependent enhancement of dengue viruses. , 2003, Advances in virus research.

[26]  R. Mischler,et al.  Inflexal V a trivalent virosome subunit influenza vaccine: production. , 2002, Vaccine.

[27]  Antonio Lanzavecchia,et al.  Maintenance of Serological Memory by Polyclonal Activation of Human Memory B Cells , 2002, Science.

[28]  K. Mozdzanowska,et al.  Complement Component C1q Enhances the Biological Activity of Influenza Virus Hemagglutinin-Specific Antibodies Depending on Their Fine Antigen Specificity and Heavy-Chain Isotype , 2002, Journal of Virology.

[29]  S Miltenyi,et al.  Correlation analysis between frequencies of circulating antigen‐specific IgG‐bearing memory B cells and serum titers of antigen‐specific IgG , 1999, European journal of immunology.

[30]  M. McHeyzer-Williams,et al.  B cell memory and the long-lived plasma cell. , 1999, Current opinion in immunology.

[31]  Keiji Fukuda,et al.  Detection of Antibody to Avian Influenza A (H5N1) Virus in Human Serum by Using a Combination of Serologic Assays , 1999, Journal of Clinical Microbiology.

[32]  K. Rajewsky,et al.  Human Immunoglobulin (Ig)M+IgD+ Peripheral Blood B Cells Expressing the CD27 Cell Surface Antigen Carry Somatically Mutated Variable Region Genes: CD27 as a General Marker for Somatically Mutated (Memory) B Cells , 1998, The Journal of experimental medicine.

[33]  R. Ahmed,et al.  Humoral immunity due to long-lived plasma cells. , 1998, Immunity.

[34]  K. Rajewsky Clonal selection and learning in the antibody system , 1996, Nature.

[35]  J. Banchereau,et al.  Generation of memory B cells and plasma cells in vitro , 1995, Science.

[36]  J. Banchereau,et al.  The CD40 antigen and its ligand. , 1994, Annual review of immunology.

[37]  J. Banchereau,et al.  Activation of human B lymphocytes through CD40 and interleukin 4 , 1989, European journal of immunology.

[38]  C. Werner‐Favre,et al.  Limiting dilution assay for human B cells based on their activation by mutant EL4 thymoma cells: total and anti‐malaria responder B cell frequencies , 1987, European journal of immunology.

[39]  T. Waldmann,et al.  Human interleukin-2 promotes proliferation of activated B cells via surface receptors similar to those of activated T cells , 1984, Nature.

[40]  B. Parodi,et al.  Activation of human B lymphocytes: frequency of antigen‐specific B cells triggered by alloreactive or by antigen‐specific T cell clones , 1983, European journal of immunology.

[41]  A. Lanzavecchia One out of five peripheral blood B lymphocytes is activated to high‐rate Ig production by human alloreactive T cell clones , 1983, European journal of immunology.