Mechanisms that determine plasma cell lifespan and the duration of humoral immunity

Summary:  Humoral immunity following vaccination or infection is mainly derived from two types of cells: memory B cells and plasma cells. Memory B cells do not actively secrete antibody but instead maintain their immunoglobulin in the membrane‐bound form that serves as the antigen‐specific B‐cell receptor. In contrast, plasma cells are terminally differentiated cells that no longer express surface‐bound immunoglobulin but continuously secrete antibody without requiring further antigenic stimulation. Pre‐existing serum or mucosal antibody elicited by plasma cells (or other intermediate antibody‐secreting cells) represents the first line of defense against reinfection and is critical for protection against many microbial diseases. However, the mechanisms involved with maintaining long‐term antibody production are not fully understood. Here, we examine several models of long‐term humoral immunity and present a new model, described as the ‘Imprinted Lifespan’ model of plasma cell longevity. The foundation of this model is that plasma cells are imprinted with a predetermined lifespan based on the magnitude of B‐cell signaling that occurs during the induction of an antigen‐specific humoral immune response. This represents a testable hypothesis and may explain why some antigen‐specific antibody responses fade over time whereas others are maintained essentially for life.

[1]  P. Nigam,et al.  Long-Lived Poxvirus Immunity, Robust CD4 Help, and Better Persistence of CD4 than CD8 T Cells , 2004, Journal of Virology.

[2]  C. Midgley,et al.  Prevalence of antibodies to Vaccinia virus after smallpox vaccination in Italy. , 2005, The Journal of general virology.

[3]  M. Leandro,et al.  Serologic changes following B lymphocyte depletion therapy for rheumatoid arthritis. , 2003, Arthritis and rheumatism.

[4]  T. Winkler,et al.  Activation of Virus-specific Memory B Cells in the Absence of T Cell Help , 2004, The Journal of experimental medicine.

[5]  D. Tarlinton,et al.  Germinal centers: form and function. , 1998, Current opinion in immunology.

[6]  S. Plotkin,et al.  Zoster in normal children after varicella vaccine. , 1989, The Journal of infectious diseases.

[7]  Y. Yueh,et al.  Measles seroepidemiology and decay rate of vaccine-induced measles IgG titers in Taiwan, 1995-1997. , 2001, Vaccine.

[8]  P. Koebel,et al.  Anatomical Origin of Dendritic Cells Determines Their Life Span in Peripheral Lymph Nodes , 2000, The Journal of Immunology.

[9]  R. A. Hale,et al.  Outbreak of smallpox in the lower Rio Grande Valley of Texas in 1949. , 1953, American journal of public health and the nation's health.

[10]  G. F. Burton,et al.  Follicular Dendritic Cells as Accessory Cells , 1990, Immunological reviews.

[11]  Lihan K. Yan,et al.  Response to smallpox vaccine in persons immunized in the distant past. , 2003, JAMA.

[12]  R. Noelle,et al.  Distinction of the memory B cell response to cognate antigen versus bystander inflammatory signals , 2009, The Journal of experimental medicine.

[13]  Kenneth G. C. Smith,et al.  Competence and competition: the challenge of becoming a long-lived plasma cell , 2006, Nature Reviews Immunology.

[14]  Rate of hemolytic antibody production by single cells in vivo in rabbits. , 1974, Journal of immunology.

[15]  R. Coffman,et al.  Therapeutic targeting of innate immunity with Toll-like receptor agonists and antagonists , 2007, Nature Medicine.

[16]  R. Ahmed,et al.  Bone marrow is a major site of long-term antibody production after acute viral infection , 1995, Journal of virology.

[17]  S. Halstead,et al.  Rubella antibody persistence after immunization. , 1982, JAMA.

[18]  E. Ward,et al.  Transcytosis and catabolism of antibody , 2002, Immunologic research.

[19]  L. Ferrucci,et al.  Immunity from smallpox vaccine persists for decades: a longitudinal study. , 2008, The American journal of medicine.

[20]  L. Genestier,et al.  The thymus-independent immunity conferred by a pneumococcal polysaccharide is mediated by long-lived plasma cells. , 2009, Blood.

[21]  R. Ahmed,et al.  SAP is required for generating long-term humoral immunity , 2003, Nature.

[22]  G. Nossal,et al.  Autoradiographic studies on the immune response. II. DNA synthesis amongst single antibody-producing cells. , 1962 .

[23]  L. Mascola,et al.  Loss of vaccine-induced immunity to varicella over time. , 2007, The New England journal of medicine.

[24]  E. Kuwert,et al.  Uptake and elimination of hepatitis B immunoglobulins after intramuscular application in man. , 1983, Developments in biological standardization.

[25]  Hyun-Dong Chang,et al.  Organization and maintenance of immunological memory by stroma niches , 2009, European journal of immunology.

[26]  J Gordon,et al.  Memory B-cell clones and the diversity of their members. , 1997, Seminars in immunology.

[27]  J. Banchereau,et al.  Follicular dendritic cells and germinal centers. , 1996, International review of cytology.

[28]  N. Adner,et al.  Pharmacokinetics of human tick-borne encephalitis virus antibody levels after injection with human tick-borne encephalitis immunoglobulin, solvent/detergent treated, FSME-BULIN S/D in healthy volunteers. , 2001, Scandinavian journal of infectious diseases.

[29]  M. Frosch,et al.  Acute and long-term effects of booster immunisation on frequencies of antigen-specific memory B-lymphocytes. , 2001, Vaccine.

[30]  S. Hansen,et al.  Duration of antiviral immunity after smallpox vaccination , 2003, Nature Medicine.

[31]  P. Schneider,et al.  Cracking the BAFF code , 2009, Nature Reviews Immunology.

[32]  M. Slifka.  Immunological memory to viral infection: Commentary , 2004 .

[33]  H. Eisen,et al.  Observations on the mechanism of secretion of gamma-globulins by isolated lymph node cells. , 1962, The Journal of biological chemistry.

[34]  J. Schooley,et al.  Autoradiographic observations of plasma cell formation. , 1961, Journal of immunology.

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

[36]  K. Calame,et al.  Regulation and functions of Blimp-1 in T and B lymphocytes. , 2008, Annual review of immunology.

[37]  T. Behrens,et al.  Relaxed Negative Selection in Germinal Centers and Impaired Affinity Maturation in bcl-x L Transgenic Mice , 1999, The Journal of experimental medicine.

[38]  Thomas F. Tedder,et al.  Maintenance of Long-Lived Plasma Cells and Serological Memory Despite Mature and Memory B Cell Depletion during CD20 Immunotherapy in Mice1 , 2008, The Journal of Immunology.

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

[40]  J. Cyster,et al.  A Coordinated Change in Chemokine Responsiveness Guides Plasma Cell Movements , 2001, The Journal of experimental medicine.

[41]  D. Klatzmann,et al.  Three populations of mouse lymph node dendritic cells with different origins and dynamics. , 1997, Journal of immunology.

[42]  I. Hardy,et al.  The incidence of zoster after immunization with live attenuated varicella vaccine. A study in children with leukemia. Varicella Vaccine Collaborative Study Group. , 1991, The New England journal of medicine.

[43]  J. Miller,et al.  AN AUTORADIOGRAPHIC STUDY OF PLASMA CELL AND LYMPHOCYTE SURVIVAL IN RAT POPLITEAL LYMPH NODES. , 1964, Journal of immunology.

[44]  O. Smithies,et al.  Antibody-producing cells in division. , 1967, Science.

[45]  D. Klinman,et al.  Varicella vaccination: Evidence for frequent reactivation of the vaccine strain in healthy children , 2000, Nature Medicine.

[46]  G. Nossal.  B lymphocyte physiology: the beginning and the end. , 1997, Ciba Foundation symposium.

[47]  S. Nutt,et al.  Terminal differentiation of lymphocytes depends on Blimp-1. , 2007, Current opinion in immunology.

[48]  Andreas Radbruch,et al.  Lifetime of plasma cells in the bone marrow , 1997, Nature.

[49]  H. Eisen,et al.  The secretion of antibody by isolated lymph node cells. , 1961, The Journal of biological chemistry.

[50]  K. Rajewsky,et al.  Persistence of memory B cells in mice deprived of T cell help. , 1990, International immunology.

[51]  W. A. Sawyer.  The Persistence of Yellow Fever Immunity. , 1931 .

[52]  K. Calame,et al.  Blimp-1 is required for maintenance of long-lived plasma cells in the bone marrow , 2005, The Journal of experimental medicine.

[53]  A. D'amico,et al.  The Development, Maturation, and Turnover Rate of Mouse Spleen Dendritic Cell Populations , 2000, The Journal of Immunology.

[54]  D. Burton.  Antibodies, viruses and vaccines , 2002, Nature Reviews Immunology.

[55]  G. Wortmann,et al.  Lack of vaccinia viremia after smallpox vaccination. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[56]  E. Joly,et al.  Capture of plasma membrane fragments from target cells by trogocytosis requires signaling in T cells but not in B cells. , 2008, Blood.

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

[58]  Dirk Homann,et al.  Differential regulation of antiviral T-cell immunity results in stable CD8+ but declining CD4+ T-cell memory , 2001, Nature Medicine.

[59]  Andreas Radbruch,et al.  Plasma Cell Survival Is Mediated by Synergistic Effects of Cytokines and Adhesion-Dependent Signals1 , 2003, The Journal of Immunology.

[60]  M. Slifka.  Immunological memory to viral infection. , 2004, Current opinion in immunology.

[61]  Donald A Henderson,et al.  Contact vaccinia--transmission of vaccinia from smallpox vaccination. , 2002, JAMA.

[62]  R. Ahmed,et al.  Limiting dilution analysis of virus-specific memory B cells by an ELISPOT assay. , 1996, Journal of immunological methods.

[63]  M. Dhalla,et al.  Treatment of severe pertussis: a study of the safety and pharmacology of intravenous pertussis immunoglobulin. , 1999, The Pediatric infectious disease journal.

[64]  R. Benner,et al.  The bone marrow: the major source of serum immunoglobulins, but still a neglected site of antibody formation. , 1981, Clinical and experimental immunology.

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

[66]  M. Sangster,et al.  Respiratory virus infection of mice provokes a permanent humoral immune response , 1994, Journal of virology.

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

[68]  Antonio Lanzavecchia,et al.  Antigen dependent and independent mechanisms that sustain serum antibody levels. , 2003, Vaccine.

[69]  E. Cooper.  Production of lymphocytes and plasma cells in the rat following immunization with human serum albumin. , 1961, Immunology.

[70]  A. Abbot,et al.  The Follicular Dendritic Cell: Long Term Antigen Retention During Immunity , 1980, Immunological reviews.

[71]  I. Maclennan,et al.  Distinct short‐lived and long‐lived antibody‐producing cell populations , 1986, European journal of immunology.

[72]  F. Klauschen,et al.  SAP-controlled T-B cell interactions underlie germinal centre formation , 2008, Nature.

[73]  R. Geha,et al.  Cutting Edge: The Dependence of Plasma Cells and Independence of Memory B Cells on BAFF and APRIL1 , 2008, The Journal of Immunology.

[74]  Mark J. Shlomchik,et al.  Maintenance of the plasma cell pool is independent of memory B cells , 2008, Proceedings of the National Academy of Sciences.

[75]  F. Stevenson,et al.  Vaccination of human subjects expands both specific and bystander memory T cells but antibody production remains vaccine specific. , 2006, Blood.

[76]  R. Zinkernagel,et al.  Induction of long-lived germinal centers associated with persisting antigen after viral infection , 1996, The Journal of experimental medicine.

[77]  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.

[78]  J. Tew,et al.  Prolonged antigen half-life in the lymphoid follicles of specifically immunized mice. , 1979, Immunology.

[79]  R. Ahmed,et al.  Long-term humoral immunity against viruses: revisiting the issue of plasma cell longevity , 1996, Trends in Microbiology.

[80]  K. Sepkowitz.  How contagious is vaccinia? , 2003, The New England journal of medicine.

[81]  G. Kelsoe,et al.  The germinal center: a crucible for lymphocyte selection. , 1996, Seminars in immunology.

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

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

[84]  O. Mäkelä,et al.  AUTORADIOGRAPHIC STUDIES ON THE IMMUNE RESPONSE , 1962, The Journal of experimental medicine.

[85]  Dan R. Littman,et al.  The Role of CXCR4 in Maintaining Peripheral B Cell Compartments and Humoral Immunity , 2004, The Journal of experimental medicine.

[86]  N. K. Jerne,et al.  Idiotypic Networks and Other Preconceived Ideas , 1984, Immunological reviews.

[87]  S. Pierce,et al.  The Agonists of TLR4 and 9 Are Sufficient to Activate Memory B Cells to Differentiate into Plasma Cells In Vitro but Not In Vivo1 , 2008, The Journal of Immunology.

[88]  W. Blackwelder,et al.  Safety and pharmacokinetic evaluation of intravenous vaccinia immune globulin in healthy volunteers. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[89]  S. Hill.  Distribution of plaque-forming cells in the mouse for a protein antigen. Evidence for highly active parathymic lymph nodes following intraperitoneal injection of hen lysozyme. , 1976, Immunology.

[90]  H. Dosch,et al.  Limiting dilution analysis of the B cell compartment in human bone marrow , 1986, European journal of immunology.

[91]  E. Joly,et al.  A very rapid and simple assay based on trogocytosis to detect and measure specific T and B cell reactivity by flow cytometry , 2006, European journal of immunology.

[92]  F. Delbos,et al.  Multiple layers of B cell memory with different effector functions , 2009, Nature Immunology.

[93]  A. Coutinho,et al.  The majority of “natural” immunoglobulin‐secreting cells are short‐lived and the progeny of cycling lymphocytes , 1987, European journal of immunology.

[94]  T. Lublin-Tennenbaum,et al.  Kinetics of formation of neutralizing antibodies against vaccinia virus following re-vaccination. , 1999, Vaccine.

[95]  Antonio Lanzavecchia,et al.  Antigen-specific interaction between T and B cells , 1985, Nature.

[96]  T. Schwartz,et al.  The persistence of neutralizing antibodies after revaccination against smallpox. , 1990, The Journal of infectious diseases.

[97]  Andreas Radbruch,et al.  Chemotactic Responsiveness Toward Ligands for CXCR3 and CXCR4 Is Regulated on Plasma Blasts During the Time Course of a Memory Immune Response1 , 2002, The Journal of Immunology.

[98]  R. Bram,et al.  BCMA Is Essential for the Survival of Long-lived Bone Marrow Plasma Cells , 2004, The Journal of experimental medicine.