Expression of Homing Receptors on IgA1 and IgA2 Plasmablasts in Blood Reflects Differential Distribution of IgA1 and IgA2 in Various Body Fluids

ABSTRACT Although secretory IgA is the most abundantly produced Ig isotype, the mechanisms underlying the differential distribution of IgA subclasses in various body fluids remain unclear. To explore these mechanisms, we examined the distribution of IgA subclasses, the influence of the nature and sites of encounters with antigens, and the correlation between IgA subclass distribution and homing potentials of circulating IgA plasmablasts. IgA1 predominated in serum, tears, nasal wash fluid, and saliva; the levels of IgA1 and IgA2 were comparable in vaginal wash fluid; and IgA2 predominated in intestinal lavage fluids. Seventy-one percent of circulating IgA plasmablasts secreted IgA1. The intestinal homing receptor (HR), α4β7, was expressed more frequently on IgA2 than on IgA1 plasmablasts, with no differences in the expression of other HRs. IgA subclass distribution among circulating antigen-specific antibody-secreting cells (ASC) was dependent on the nature of the antigen: following vaccination with Salmonella enterica serovar Typhi, unconjugated pneumococcal polysaccharide, or Haemophilus influenzae polysaccharide-diphtheria toxoid conjugate, the proportions of specific IgA1 ASC were 74%, 47%, 56%, and 80%, respectively. HR expression depended on the route of administration: expression of HRs was different after oral than after parenteral vaccination, while no difference was seen between HR expression of antigen-specific IgA1 and IgA2 ASC induced via the same route. The key factors determining IgA subclass distribution in a given secretion are the nature of the antigens encountered at a particular site and the site-specific homing instructions given to lymphocytes at that site. These two factors are reflected as differences in the homing profiles of the total populations of circulating IgA1 and IgA2 plasmablasts.

[1]  T. Reunala,et al.  Decreased numbers of circulating plasmablasts and differences in IgA1‐plasmablast homing to skin in coeliac disease and dermatitis herpetiformis , 2009, Clinical and experimental immunology.

[2]  A. Kantele,et al.  Distinctive homing profile of pathogen-specific activated lymphocytes in human urinary tract infection. , 2008, Clinical immunology.

[3]  J. Mora,et al.  Vitamin effects on the immune system: vitamins A and D take centre stage , 2008, Nature Reviews Immunology.

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

[5]  A. Macpherson,et al.  The functional interactions of commensal bacteria with intestinal secretory IgA , 2007, Current opinion in gastroenterology.

[6]  P. Brandtzaeg.  Induction of secretory immunity and memory at mucosal surfaces. , 2007, Vaccine.

[7]  H. Tlaskalova-Hogenova,et al.  The Role of Mucosal Microbiota in the Development, Maintenance, and Pathologies of the Mucosal Immune System , 2005, Mucosal Immunology.

[8]  J. Mestecky,et al.  Human Male Genital Tract Secretions: Both Mucosal and Systemic Immune Compartments Contribute to the Humoral Immunity1 , 2005, The Journal of Immunology.

[9]  P. Brandtzaeg,et al.  Mucosal B cells: phenotypic characteristics, transcriptional regulation, and homing properties , 2005, Immunological reviews.

[10]  S. Jalkanen,et al.  Lymphocyte homing to the gut: attraction, adhesion, and commitment , 2005, Immunological reviews.

[11]  J. Woof,et al.  Mucosal immunoglobulins , 2005, Immunological reviews.

[12]  A. Kantele,et al.  Cutaneous lymphocyte antigen expression on human effector B cells depends on the site and on the nature of antigen encounter , 2003, European journal of immunology.

[13]  S. Michalek,et al.  Effect of age on immunoglobulin A subclass distribution in human parotid saliva. , 2003, Oral microbiology and immunology.

[14]  E. Kunkel,et al.  Plasma-cell homing , 2003, Nature Reviews Immunology.

[15]  Baohui Xu,et al.  Lymphocyte Homing to Bronchus-associated Lymphoid Tissue (BALT) Is Mediated by L-selectin/PNAd, α4β1 Integrin/VCAM-1, and LFA-1 Adhesion Pathways , 2003, The Journal of experimental medicine.

[16]  M. Mayo,et al.  Limited Local and Systemic Antibody Responses toNeisseria gonorrhoeae during Uncomplicated Genital Infections , 1999, Infection and Immunity.

[17]  A. Kantele,et al.  Homing potentials of circulating antibody-secreting cells after administration of oral or parenteral protein or polysaccharide vaccine in humans. , 1999, Vaccine.

[18]  R. Alvarez,et al.  Differences in Immune Responses Induced by Oral and Rectal Immunizations with Salmonella typhi Ty21a: Evidence for Compartmentalization within the Common Mucosal Immune System in Humans , 1998, Infection and Immunity.

[19]  E. Butcher,et al.  Homing potentials of circulating lymphocytes in humans depend on the site of activation: oral, but not parenteral, typhoid vaccination induces circulating antibody-secreting cells that all bear homing receptors directing them to the gut. , 1997, Journal of immunology.

[20]  J. Mestecky,et al.  Variations in immunoglobulins and IgA subclasses of human uterine cervical secretions around the time of ovulation , 1996, Clinical and experimental immunology.

[21]  A. Kantele,et al.  Circulating immunoglobulin‐secreting cells are heterogeneous in their expression of maturation markers and homing receptors , 1996, Clinical and experimental immunology.

[22]  S. Jalkanen,et al.  Mucosally activated circulating human B cells in diarrhea express homing receptors directing them back to the gut. , 1996, Gastroenterology.

[23]  J. Kral,et al.  Intestinal B-cell isotype response in relation to local bacterial load: evidence for immunoglobulin A subclass adaptation. , 1995, Gastroenterology.

[24]  J. Banchereau,et al.  Human circulating specific antibody‐forming cells after systemic and mucosal immunizations: differential homing commitments and cell surface differentiation markers , 1995, European journal of immunology.

[25]  E. Berg,et al.  α4β7 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1 , 1993, Cell.

[26]  P. Small,et al.  Passive transfer of local immunity to influenza virus infection by IgA antibody. , 1991, Journal of immunology.

[27]  R Weltzin,et al.  New model for analysis of mucosal immunity: intestinal secretion of specific monoclonal immunoglobulin A from hybridoma tumors protects against Vibrio cholerae infection , 1991, Infection and immunity.

[28]  L. Picker,et al.  ELAM-1 is an adhesion molecule for skin-homing T cells , 1991, Nature.

[29]  A. Kantele,et al.  Comparison of the human immune response to live oral, killed oral or killed parenteral Salmonella typhi TY21A vaccines. , 1991, Microbial pathogenesis.

[30]  T. Nagamine,et al.  Functional role of respiratory tract haemagglutinin-specific IgA antibodies in protection against influenza. , 1990, Vaccine.

[31]  J. Mestecky,et al.  Secretory immunoglobulin A carries oligosaccharide receptors for Escherichia coli type 1 fimbrial lectin , 1990, Infection and immunity.

[32]  A. Kantele.  Antibody-secreting cells in the evaluation of the immunogenicity of an oral vaccine. , 1990, Vaccine.

[33]  J. Mcghee,et al.  Immunization of humans with polysaccharide vaccines induces systemic, predominantly polymeric IgA2-subclass antibody responses. , 1990, Journal of immunology.

[34]  E. Butcher,et al.  Identification of a human peripheral lymph node homing receptor: a rapidly down-regulated adhesion molecule. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[35]  I. Stamenkovic,et al.  Leu-8/TQ1 is the human equivalent of the Mel-14 lymph node homing receptor , 1989, Nature.

[36]  J. Mestecky,et al.  IgA subclasses of human colostral antibodies specific for microbial and food antigens. , 1989, Clinical and experimental immunology.

[37]  P. Brandtzaeg,et al.  J-chain expression is more prominent in immunoglobulin A2 than in immunoglobulin A1 colonic immunocytes and is decreased in both subclasses associated with inflammatory bowel disease. , 1988, Gastroenterology.

[38]  J. Mestecky,et al.  Systemic immunization with pneumococcal polysaccharide vaccine induces a predominant IgA2 response of peripheral blood lymphocytes and increases of both serum and secretory anti-pneumococcal antibodies. , 1988, Journal of immunology.

[39]  K. Hatch,et al.  Secretory immune system of the female reproductive tract: I. Immunoglobulin and secretory component‐containing cells , 1988, Obstetrics and gynecology.

[40]  D. Delacroix,et al.  Intravascular and mucosal immunoglobulin A: two separate but related systems of immune defense? , 1987, Annals of internal medicine.

[41]  P. Brandtzaeg,et al.  Different subclass distribution of IgA-producing cells in human lymphoid organs and various secretory tissues. , 1986, Journal of immunology.

[42]  J. Mestecky,et al.  Molecular forms of tear IgA and distribution of IgA subclasses in human lacrimal glands. , 1985, The Journal of allergy and clinical immunology.

[43]  J. Mestecky,et al.  Immunoglobulin A subclass distribution of naturally occurring salivary antibodies to microbial antigens , 1985, Infection and immunity.

[44]  J. Mestecky,et al.  Distribution of IgA1-, IgA2-, and J chain-containing cells in human tissues. , 1984, Journal of immunology.

[45]  J. Rambaud,et al.  IgA subclasses in various secretions and in serum. , 1982, Immunology.

[46]  C. Griscelli,et al.  THE DISTRIBUTION OF LARGE DIVIDING LYMPH NODE CELLS IN SYNGENEIC RECIPIENT RATS AFTER INTRAVENOUS INJECTION , 1969, The Journal of experimental medicine.

[47]  E. J. Knight,et al.  The route of re-circulation of lymphocytes in the rat , 1964, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[48]  M. Kilian,et al.  Chapter 15 – Microbial Evasion of IgA Functions , 2005 .

[49]  M. Kerr,et al.  Chapter 9 – Mucosal Immunoglobulins , 2005 .

[50]  J. McVernon,et al.  T helper cells and efficacy of Haemophilus influenzae type b conjugate vaccination. , 2004, The Lancet. Infectious diseases.

[51]  Tasuku Honjo,et al.  Intestinal IgA synthesis: regulation of front-line body defences , 2003, Nature Reviews Immunology.

[52]  J. Mestecky,et al.  IgA subclasses. , 1986, Monographs in allergy.