tetano
Editor, Senior Moderator
Sci Transl Med. 2018 Feb 14;10(428). pii: eaan8405. doi: 10.1126/scitranslmed.aan8405.
[h=1]Circulating TFH cells, serological memory, and tissue compartmentalization shape human influenza-specific B cell immunity.[/h] Koutsakos M[SUP]1[/SUP], Wheatley AK[SUP]1[/SUP], Loh L[SUP]1[/SUP], Clemens EB[SUP]1[/SUP], Sant S[SUP]1[/SUP], N?ssing S[SUP]1[/SUP], Fox A[SUP]1[/SUP], Chung AW[SUP]1[/SUP], Laurie KL[SUP]2[/SUP], Hurt AC[SUP]2[/SUP], Rockman S[SUP]1,[/SUP][SUP]3[/SUP], Lappas M[SUP]4[/SUP], Loudovaris T[SUP]5[/SUP], Mannering SI[SUP]5[/SUP], Westall GP[SUP]6[/SUP], Elliot M[SUP]7,[/SUP][SUP]8[/SUP], Tangye SG[SUP]9,[/SUP][SUP]10[/SUP], Wakim LM[SUP]1[/SUP], Kent SJ[SUP]1,[/SUP][SUP]11,[/SUP][SUP]12[/SUP], Nguyen THO[SUP]13[/SUP], Kedzierska K[SUP]13[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Immunization with the inactivated influenza vaccine (IIV) remains the most effective strategy to combat seasonal influenza infections. IIV activates B cells and T follicular helper (T[SUB]FH[/SUB]) cells and thus engenders antibody-secreting cells and serum antibody titers. However, the cellular events preceding generation of protective immunity in humans are inadequately understood. We undertook an in-depth analysis of B cell and T cell immune responses to IIV in 35 healthy adults. Using recombinant hemagglutinin (rHA) probes to dissect the quantity, phenotype, and isotype of influenza-specific B cells against A/California09-H1N1, A/Switzerland-H3N2, and B/Phuket, we showed that vaccination induced a three-pronged B cell response comprising a transient CXCR5[SUP]-[/SUP]CXCR3[SUP]+[/SUP] antibody-secreting B cell population, CD21[SUP]hi[/SUP]CD27[SUP]+[/SUP] memory B cells, and CD21[SUP]lo[/SUP]CD27[SUP]+[/SUP] B cells. Activation of circulating T[SUB]FH[/SUB] cells correlated with the development of both CD21[SUP]lo[/SUP] and CD21[SUP]hi[/SUP] memory B cells. However, preexisting antibodies could limit increases in serum antibody titers. IIV had no marked effect on CD8[SUP]+[/SUP], mucosal-associated invariant T, γδ T, and natural killer cell activation. In addition, vaccine-induced B cells were not maintained in peripheral blood at 1 year after vaccination. We provide a dissection of rHA-specific B cells across seven human tissue compartments, showing that influenza-specific memory (CD21[SUP]hi[/SUP]CD27[SUP]+[/SUP]) B cells primarily reside within secondary lymphoid tissues and the lungs. Our study suggests that a rational design of universal vaccines needs to consider circulating T[SUB]FH[/SUB] cells, preexisting serological memory, and tissue compartmentalization for effective B cell immunity, as well as to improve targeting cellular T cell immunity.
PMID: 29444980 DOI: 10.1126/scitranslmed.aan8405
[h=1]Circulating TFH cells, serological memory, and tissue compartmentalization shape human influenza-specific B cell immunity.[/h] Koutsakos M[SUP]1[/SUP], Wheatley AK[SUP]1[/SUP], Loh L[SUP]1[/SUP], Clemens EB[SUP]1[/SUP], Sant S[SUP]1[/SUP], N?ssing S[SUP]1[/SUP], Fox A[SUP]1[/SUP], Chung AW[SUP]1[/SUP], Laurie KL[SUP]2[/SUP], Hurt AC[SUP]2[/SUP], Rockman S[SUP]1,[/SUP][SUP]3[/SUP], Lappas M[SUP]4[/SUP], Loudovaris T[SUP]5[/SUP], Mannering SI[SUP]5[/SUP], Westall GP[SUP]6[/SUP], Elliot M[SUP]7,[/SUP][SUP]8[/SUP], Tangye SG[SUP]9,[/SUP][SUP]10[/SUP], Wakim LM[SUP]1[/SUP], Kent SJ[SUP]1,[/SUP][SUP]11,[/SUP][SUP]12[/SUP], Nguyen THO[SUP]13[/SUP], Kedzierska K[SUP]13[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Immunization with the inactivated influenza vaccine (IIV) remains the most effective strategy to combat seasonal influenza infections. IIV activates B cells and T follicular helper (T[SUB]FH[/SUB]) cells and thus engenders antibody-secreting cells and serum antibody titers. However, the cellular events preceding generation of protective immunity in humans are inadequately understood. We undertook an in-depth analysis of B cell and T cell immune responses to IIV in 35 healthy adults. Using recombinant hemagglutinin (rHA) probes to dissect the quantity, phenotype, and isotype of influenza-specific B cells against A/California09-H1N1, A/Switzerland-H3N2, and B/Phuket, we showed that vaccination induced a three-pronged B cell response comprising a transient CXCR5[SUP]-[/SUP]CXCR3[SUP]+[/SUP] antibody-secreting B cell population, CD21[SUP]hi[/SUP]CD27[SUP]+[/SUP] memory B cells, and CD21[SUP]lo[/SUP]CD27[SUP]+[/SUP] B cells. Activation of circulating T[SUB]FH[/SUB] cells correlated with the development of both CD21[SUP]lo[/SUP] and CD21[SUP]hi[/SUP] memory B cells. However, preexisting antibodies could limit increases in serum antibody titers. IIV had no marked effect on CD8[SUP]+[/SUP], mucosal-associated invariant T, γδ T, and natural killer cell activation. In addition, vaccine-induced B cells were not maintained in peripheral blood at 1 year after vaccination. We provide a dissection of rHA-specific B cells across seven human tissue compartments, showing that influenza-specific memory (CD21[SUP]hi[/SUP]CD27[SUP]+[/SUP]) B cells primarily reside within secondary lymphoid tissues and the lungs. Our study suggests that a rational design of universal vaccines needs to consider circulating T[SUB]FH[/SUB] cells, preexisting serological memory, and tissue compartmentalization for effective B cell immunity, as well as to improve targeting cellular T cell immunity.
PMID: 29444980 DOI: 10.1126/scitranslmed.aan8405