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Modeling the Dynamics and Migratory Pathways of Virus-Specific Antibody-Secreting Cell Populations in Primary Influenza Infection

Journal Article · · PLoS ONE
 [1];  [2];  [2];  [2];  [2];  [2];  [2];  [2];  [3];  [2];  [2]
  1. University of Rochester, NY (United States); DOE/OSTI
  2. University of Rochester, NY (United States)
  3. Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
+ Show Author Affiliations
The B cell response to influenza infection of the respiratory tract contributes to viral clearance and establishes profound resistance to reinfection by related viruses. Numerous studies have measured virus-specific antibody-secreting cell (ASC) frequencies in different anatomical compartments after influenza infection and provided a general picture of the kinetics of ASC formation and dispersion. However, the dynamics of ASC populations are difficult to determine experimentally and have received little attention. Here, we applied mathematical modeling to investigate the dynamics of ASC growth, death, and migration over the 2-week period following primary influenza infection in mice. Experimental data for model fitting came from high frequency measurements of virus-specific IgM, IgG, and IgA ASCs in the mediastinal lymph node (MLN), spleen, and lung. Model construction was based on a set of assumptions about ASC gain and loss from the sampled sites, and also on the directionality of ASC trafficking pathways. Most notably, modeling results suggest that differences in ASC fate and trafficking patterns reflect the site of formation and the expressed antibody class. Essentially all early IgA ASCs in the MLN migrated to spleen or lung, whereas cell death was likely the major reason for IgM and IgG ASC loss from the MLN. In contrast, the spleen contributed most of the IgM and IgG ASCs that migrated to the lung, but essentially none of the IgA ASCs. This finding points to a critical role for regional lymph nodes such as the MLN in the rapid generation of IgA ASCs that seed the lung. Results for the MLN also suggest that ASC death is a significant early feature of the B cell response. Overall, our analysis is consistent with accepted concepts in many regards, but it also indicates novel features of the B cell response to influenza that warrant further investigation.
Research Organization:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Organization:
National Institute of Allergy and Infectious Diseases; USDOE Office of Science (SC), Biological and Environmental Research (BER)
Grant/Contract Number:
AC52-06NA25396
OSTI ID:
1627722
Journal Information:
PLoS ONE, Journal Name: PLoS ONE Journal Issue: 8 Vol. 9; ISSN 1932-6203
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
B cells
cell death
cell differentiation
influenza
influenza viruses
lymph nodes
respiratory infections
spleen