Research Article Persistent Polyclonal B Cell Lymphocytosis B Cells Can Be Activated through CD40-CD154 Interaction Emmanuelle Dugas-Bourdages, 1 Sonia Néron, 2,3 Annie Roy, 2 André Darveau, 3 and Robert Delage 1 1 Centre Universitaire d’H´ ematologie et d’Oncologie de Qu´ ebec, CHU de Qu´ ebec, Hˆ opital de l’Enfant-J´ esus, 1401 18i` eme rue, Qu´ ebec, QC, Canada G1J 1Z4 2 H´ ema-Qu´ ebec, Recherche et D´ eveloppement, 1070 avenue des Sciences-de-la-Vie, Qu´ ebec, QC, Canada G1V 5C3 3 D´ epartement de Biochimie, de Microbiologie et de Bio-Informatique, Pavillon Alexandre-Vachon, 1045 avenue de la M´ edecine, Bureau 3428, Universit´ e Laval, Qu´ ebec, QC, Canada G1V 0A6 Correspondence should be addressed to Robert Delage; robert.delage@fmed.ulaval.ca Received 21 July 2014; Revised 19 November 2014; Accepted 20 November 2014; Published 14 December 2014 Academic Editor: Emili Montserrat Copyright © 2014 Emmanuelle Dugas-Bourdages et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Persistent polyclonal B cell lymphocytosis (PPBL) is a rare disorder, diagnosed primarily in adult female smokers and characterized by an expansion of CD19 + CD27 + IgM + memory B cells, by the presence of binucleated lymphocytes, and by a moderate elevation of serum IgM. e clinical course is usually benign, but it is not known whether or not PPBL might be part of a process leading to the emergence of a malignant proliferative disorder. In this study we sought to investigate the functional response of B cells from patients with PPBL by use of an optimal memory B cell culture model based on the CD40-CD154 interaction. We found that the proliferation of PPBL B cells was almost as important as that of B cells from normal controls, resulting in high immunoglobulin secretion with in vitro isotypic switching. We conclude that the CD40-CD154 activation pathway is functional in the memory B cell population of PPBL patients, suggesting that the disorder may be due to either a dysfunction of other cells in the microenvironment or a possible defect in another B cell activation pathway. 1. Introduction Persistent polyclonal B cell lymphocytosis (PPBL) is a rare and presumably nonmalignant lymphoproliferative disorder diagnosed predominantly in women [1, 2], although a few men have also been diagnosed with this condition [3–5]. Clinical symptoms are nonspecific except for mild fatigue in most individuals with this disorder [1, 6]. Patients, usually cigarette smokers, present with elevated polyclonal serum IgM and a persistent polyclonal lymphocytosis of memory B cell origin as evidenced, on flow cytometry, by a population of CD27 + IgM + IgD + cells with normal / ratio [7–11] repre- senting more than 70% of their total B lymphocytes [12]. e blood smear in these patients is characterized by the presence of mostly atypical lymphocytes with abundant cytoplasm and mature nuclei. Binuclearity can be observed in 1–9% of their lymphocytes [13]. Patients predominantly express the HLA- DR7 phenotype, while this particular allele usually occurs in only 26% of the normal Caucasian population [14]. e clinical course is usually benign, but we have pre- viously described the case of one individual who developed a diffuse large-B-cell lymphoma (DLBCL) 19 years aſter a diagnosis of PPBL [15]. Overall, a small proportion of patients with PPBL has been reported in the literature to have developed a malignant disease [16–18]. Although the pathophysiology of this disorder remains largely unknown, a familial link is one of its constant features, suggesting the existence of an underlying genetic defect [19]. Despite the apparent polyclonal nature of the B cell proliferation, the frequency of rearrangements between the bcl-2 and Ig heavy chain genes is 100-fold greater than that observed in normal Hindawi Publishing Corporation Advances in Hematology Volume 2014, Article ID 854124, 10 pages http://dx.doi.org/10.1155/2014/854124