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Blood, 1 September 2006, Vol. 108, No. 5, pp. 1580-1587.
Prepublished online as a Blood First Edition Paper on April 27, 2006; DOI 10.1182/blood-2005-11-013383.
 Previous Article | Next Article 
Submitted November 7, 2005
Accepted April 17, 2006
Loss of memory B cells impairs maintenance of long-term
serological memory during HIV-1 infection
Kehmia Titanji, Angelo De Milito, Alberto Cagigi, Rigmor Thorstensson, Sven Grutzmeier, Ann Atlas, Bo Hejdeman, Frank P Kroon, Lucia Lopalco, Anna Nilsson, and Francesca Chiodi*
Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden
Swedish Institute for Disease Control, Solna, Sweden
Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden
Department of Infectious Diseases, Leiden University Medical Center, Netherlands
Infectious Disease Clinic, San Raffaele Scientific Institute, Milan, Italy
* Corresponding author; email: francesca.chiodi{at}mtc.ki.se.
Circulating memory B cells are severely reduced in the
peripheral blood of HIV-1 infected patients. We
investigated whether dysfunctional serological memory to
non-HIV antigens is related to disease progression by
evaluating the frequency of memory B cells, plasma IgG,
plasma levels of antibodies to measles and Streptococcus
pneumoniae, and enumerating measles-specific antibody-
secreting cells in patients with primary, chronic and
long-term non-progressive HIV-1 infection. We also
evaluated the in vitro production of IgM and IgG
antibodies against measles and S.pneumoniae antigens
following polyclonal activation of PBMC from patients.
The percentage of memory B cells correlated with CD4+ T
cell counts in patients, thus representing a marker of
disease progression. While patients with primary and
chronic infection had severe defects in serological
memory, long-term non-progressors had memory B cell
frequency and levels of antigen-specific antibodies
comparable to controls. We also evaluated the effect of
antiretroviral therapy on these serological memory
defects and found that antiretroviral therapy did not
restore serological memory in primary nor in chronic
infection. We suggest that HIV infection impairs
maintenance of long-term serological immunity to HIV-1-
unrelated antigens and this defect is initiated early in
infection. This may have important consequences for the
response of HIV-infected patients to immunizations.
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