PMID- 18250444
OWN - NLM
STAT- MEDLINE
DCOM- 20080417
LR  - 20190516
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 180
IP  - 4
DP  - 2008 Feb 15
TI  - Porcine reproductive and respiratory syndrome virus subverts repertoire 
      development by proliferation of germline-encoded B cells of all isotypes bearing 
      hydrophobic heavy chain CDR3.
PG  - 2347-56
AB  - Isolator piglets infected with porcine reproductive and respiratory syndrome 
      virus (PRRSV), which is related to the lactate dehydrogenase-elevating virus of 
      mice, develop severe hypergammaglobulinemia, lymph node adenopathy, and 
      autoimmune disease. Many of the polyclonally activated B cell clones bear 
      hydrophobic H chain CDR3s (HCDR3s) and are disseminated to most lymphoid tissues. 
      We show in this study that B cells with identical hydrophobic HCDR3s are 
      expressed with all major isotypes in PRRSV-infected piglets (PIPs), explaining 
      why PRRSV-induced hypergammaglobulinemia is seen in all major isotypes. Up to 
      one-third of randomly selected VDJ clones from the respiratory tract of PIPs have 
      hydrophobic HCDR3s exclusively bearing VDJ rearrangements with CDR1, CDR2, and 
      nearly intact DH segments in germline configuration. These HCDR3s are long and 
      D(H)A and D(H)B are exclusively used in reading frame 3. A minimal tripeptide 
      motif containing three hydrophobic amino acids (Leu, Val, and Ile) or any two 
      plus alanine is common to this hydrophobic patch. We propose that PRRSV infection 
      causes generalized Ag-independent B cell activation and hypergammaglobulinemia 
      with biased expansion of a subpopulation of the preimmune repertoire with 
      hydrophobic binding sites that normally disappears during Ag-driven repertoire 
      diversification. Elevated Ig levels in PIP cannot be explained as antiviral Abs; 
      some Igs can account for autoantibodies to dsDNA and Golgi, whereas those with 
      hydrophobic binding sites may account for the Ig aggregates seen in PIPs and 
      lactate dehydrogenase-elevating virus-infected mice. This diversion from normal 
      repertoire development may explain the delayed immune response to PRRSV.
FAU - Butler, John E
AU  - Butler JE
AD  - Department of Microbiology, University of Iowa Medical School, 51 Newton Road, 
      Iowa City, IA 52242, USA. john-butler@uiowa.edu
FAU - Wertz, Nancy
AU  - Wertz N
FAU - Weber, Patrick
AU  - Weber P
FAU - Lager, Kelly M
AU  - Lager KM
LA  - eng
SI  - GENBANK/EU267244
SI  - GENBANK/EU267245
SI  - GENBANK/EU267246
SI  - GENBANK/EU267247
SI  - GENBANK/EU267248
SI  - GENBANK/EU267249
SI  - GENBANK/EU267250
SI  - GENBANK/EU267251
SI  - GENBANK/EU267252
SI  - GENBANK/EU267253
SI  - GENBANK/EU267254
SI  - GENBANK/EU267255
SI  - GENBANK/EU267256
SI  - GENBANK/EU267257
SI  - GENBANK/EU267258
SI  - GENBANK/EU267259
SI  - GENBANK/EU267260
SI  - GENBANK/EU267261
SI  - GENBANK/EU267262
SI  - GENBANK/EU267263
SI  - GENBANK/EU267264
SI  - GENBANK/EU267265
SI  - GENBANK/EU267266
SI  - GENBANK/EU267267
SI  - GENBANK/EU267268
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Complementarity Determining Regions)
RN  - 0 (Immunoglobulin Heavy Chains)
RN  - 0 (Immunoglobulin Isotypes)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - B-Lymphocyte Subsets/*cytology/immunology/metabolism/virology
MH  - Cell Differentiation/genetics/*immunology
MH  - *Cell Proliferation
MH  - Clone Cells
MH  - Complementarity Determining Regions/*biosynthesis/genetics
MH  - Germ Cells/*cytology/immunology/metabolism/virology
MH  - Hydrophobic and Hydrophilic Interactions
MH  - Immunoglobulin Heavy Chains/*biosynthesis/genetics
MH  - Immunoglobulin Isotypes/*biosynthesis/genetics
MH  - Molecular Sequence Data
MH  - Porcine Reproductive and Respiratory Syndrome/immunology/pathology
MH  - Porcine respiratory and reproductive syndrome virus/*immunology
MH  - Random Allocation
MH  - Somatic Hypermutation, Immunoglobulin
MH  - Swine
EDAT- 2008/02/06 09:00
MHDA- 2008/04/18 09:00
CRDT- 2008/02/06 09:00
PHST- 2008/02/06 09:00 [pubmed]
PHST- 2008/04/18 09:00 [medline]
PHST- 2008/02/06 09:00 [entrez]
AID - 180/4/2347 [pii]
AID - 10.4049/jimmunol.180.4.2347 [doi]
PST - ppublish
SO  - J Immunol. 2008 Feb 15;180(4):2347-56. doi: 10.4049/jimmunol.180.4.2347.