PMID- 25407649
OWN - NLM
STAT- MEDLINE
DCOM- 20150805
LR  - 20181113
IS  - 1559-0755 (Electronic)
IS  - 0257-277X (Linking)
VI  - 60
IP  - 2-3
DP  - 2014 Dec
TI  - Intravenous immunoglobulin replacement therapy in common variable 
      immunodeficiency induces B cell depletion through differentiation into 
      apoptosis-prone CD21(low) B cells.
PG  - 330-8
LID - 10.1007/s12026-014-8599-8 [doi]
AB  - Intravenous immunoglobulin (IVIG), besides its use as replacement therapy in 
      patients with antibody deficiencies, is broadly used as an immunomodulatory agent 
      for the treatment of autoimmune and inflammatory disorders. The mechanisms of 
      action of IVIG include Fc receptor blockade, inhibition of cytokines and growth 
      factors, modulation of macrophages and dendritic cells, enhancement of regulatory 
      T cells, and modulation of B cells through the FcgammaRIIB receptor and CD22. Recent 
      studies suggest that in vitro exposure of human B cells to IVIG determines 
      functional changes reminiscent of anergy and that IVIG treatment of patients with 
      common variable immunodeficiency (CVID) induces in B cells ERK activation, a 
      feature of anergy. Here, we show that IVIG therapy drives the B cells of patients 
      with CVID to down-regulate CD21 expression and to assume the peculiar phenotype 
      of the anergic-like, apoptosis-prone CD21(low) B cells that are spontaneously 
      expanded in a subset of CVID and in some other immunological disorders. The 
      CD21(low) B cells newly generated after IVIG infusion undergo spontaneous 
      apoptosis upon in vitro culture. Furthermore, IVIG infusion is rapidly followed 
      by a significant, although discrete, decrease in the number of circulating B 
      cells, but not of T cells or of natural killer cells. These findings suggest that 
      IVIG therapy may constrain antibody responses by inducing B cell depletion 
      through differentiation into CD21(low) B cells that undergo accelerated 
      apoptosis.
FAU - Mitrevski, Milica
AU  - Mitrevski M
AD  - Department of Clinical Medicine, Sapienza University of Rome, Viale 
      dell'Universita 37, 00185, Rome, Italy.
FAU - Marrapodi, Ramona
AU  - Marrapodi R
FAU - Camponeschi, Alessandro
AU  - Camponeschi A
FAU - Lazzeri, Cristina
AU  - Lazzeri C
FAU - Todi, Laura
AU  - Todi L
FAU - Quinti, Isabella
AU  - Quinti I
FAU - Fiorilli, Massimo
AU  - Fiorilli M
FAU - Visentini, Marcella
AU  - Visentini M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Immunol Res
JT  - Immunologic research
JID - 8611087
RN  - 0 (Immunoglobulins, Intravenous)
RN  - 0 (Receptors, Complement 3d)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Apoptosis/*drug effects/*immunology
MH  - B-Lymphocytes/drug effects/*immunology/metabolism
MH  - Common Variable Immunodeficiency/*drug therapy/*immunology
MH  - Female
MH  - Humans
MH  - Immunoglobulins, Intravenous/pharmacology/*therapeutic use
MH  - Immunophenotyping
MH  - Lymphocyte Count
MH  - *Lymphocyte Depletion
MH  - Male
MH  - Middle Aged
MH  - Phenotype
MH  - Receptors, Complement 3d/metabolism
EDAT- 2014/11/20 06:00
MHDA- 2015/08/06 06:00
CRDT- 2014/11/20 06:00
PHST- 2014/11/20 06:00 [entrez]
PHST- 2014/11/20 06:00 [pubmed]
PHST- 2015/08/06 06:00 [medline]
AID - 10.1007/s12026-014-8599-8 [doi]
PST - ppublish
SO  - Immunol Res. 2014 Dec;60(2-3):330-8. doi: 10.1007/s12026-014-8599-8.