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Persistent Polyclonal B Cell Lymphocytosis B Cells Can Be Activated through CD40-CD154 Interaction.

Dugas-Bourdages E, Néron S, Roy A, Darveau A, Delage R - Adv Hematol (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Centre Universitaire d'Hématologie et d'Oncologie de Québec, CHU de Québec, Hôpital de l'Enfant-Jésus, 1401 18ième rue, Québec, QC, Canada G1J 1Z4.

ABSTRACT
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. The 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.

No MeSH data available.


Related in: MedlinePlus

Isotype switching during culture of PPBL B cells with low CD154 interaction. The IgG and IgM secretion ratios of PPBL CD19+ cells stimulated with a low level of CD154 interaction were determined by ELISA in supernatant collected after 5 days (5 d) and evaluated on day 14 (14 d), for all patient samples. Four healthy controls submitted to identical culture conditions (HC) were analyzed similarly and data is presented as the mean ± SD.
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fig5: Isotype switching during culture of PPBL B cells with low CD154 interaction. The IgG and IgM secretion ratios of PPBL CD19+ cells stimulated with a low level of CD154 interaction were determined by ELISA in supernatant collected after 5 days (5 d) and evaluated on day 14 (14 d), for all patient samples. Four healthy controls submitted to identical culture conditions (HC) were analyzed similarly and data is presented as the mean ± SD.

Mentions: Based on the above results, flow cytometry analyses of CD40-activated PPBL B cells were performed in order to monitor their expression of IgG (Figure 4(a)). It was thus found that a heightened proportion of IgM−IgD− B cells correlated quite precisely with the emergence of IgG+ B cells. Furthermore, high IgG secretion rates, similar to those observed in control B cells, were observed in CD40-activated B cells from the six PPBL patient samples (Figure 4(b)). Conversely, IgM secretion rates within PPBL B cells were higher than those seen in control B cells, in concordance with the higher proportion of IgM+ cells. In addition, the capacity of PPBL B cells to switch isotypes and to secrete IgG suggests that their in vitro response to CD40 is similar to that of normal B cells. Another proof of the in vitro isotype switching capacity of PPBL B cells is in the observed difference between IgM/IgG ratios at days 5 and 14 for cultures in a low interaction CD40-CD154 medium. On day 5, the IgM/IgG ratio of PPBL B cells varied between 6 and 205, whereas at the end of the cultures (day 14), the IgM/IgG ratio was nearly or completely reversed in favour of IgG (0,4 to 3,5) (Figure 5). These observations are in agreement with the reported isotype switching capacity of normal CD27+IgD+IgM+ human B cells [35].


Persistent Polyclonal B Cell Lymphocytosis B Cells Can Be Activated through CD40-CD154 Interaction.

Dugas-Bourdages E, Néron S, Roy A, Darveau A, Delage R - Adv Hematol (2014)

Isotype switching during culture of PPBL B cells with low CD154 interaction. The IgG and IgM secretion ratios of PPBL CD19+ cells stimulated with a low level of CD154 interaction were determined by ELISA in supernatant collected after 5 days (5 d) and evaluated on day 14 (14 d), for all patient samples. Four healthy controls submitted to identical culture conditions (HC) were analyzed similarly and data is presented as the mean ± SD.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4279877&req=5

fig5: Isotype switching during culture of PPBL B cells with low CD154 interaction. The IgG and IgM secretion ratios of PPBL CD19+ cells stimulated with a low level of CD154 interaction were determined by ELISA in supernatant collected after 5 days (5 d) and evaluated on day 14 (14 d), for all patient samples. Four healthy controls submitted to identical culture conditions (HC) were analyzed similarly and data is presented as the mean ± SD.
Mentions: Based on the above results, flow cytometry analyses of CD40-activated PPBL B cells were performed in order to monitor their expression of IgG (Figure 4(a)). It was thus found that a heightened proportion of IgM−IgD− B cells correlated quite precisely with the emergence of IgG+ B cells. Furthermore, high IgG secretion rates, similar to those observed in control B cells, were observed in CD40-activated B cells from the six PPBL patient samples (Figure 4(b)). Conversely, IgM secretion rates within PPBL B cells were higher than those seen in control B cells, in concordance with the higher proportion of IgM+ cells. In addition, the capacity of PPBL B cells to switch isotypes and to secrete IgG suggests that their in vitro response to CD40 is similar to that of normal B cells. Another proof of the in vitro isotype switching capacity of PPBL B cells is in the observed difference between IgM/IgG ratios at days 5 and 14 for cultures in a low interaction CD40-CD154 medium. On day 5, the IgM/IgG ratio of PPBL B cells varied between 6 and 205, whereas at the end of the cultures (day 14), the IgM/IgG ratio was nearly or completely reversed in favour of IgG (0,4 to 3,5) (Figure 5). These observations are in agreement with the reported isotype switching capacity of normal CD27+IgD+IgM+ human B cells [35].

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Centre Universitaire d'Hématologie et d'Oncologie de Québec, CHU de Québec, Hôpital de l'Enfant-Jésus, 1401 18ième rue, Québec, QC, Canada G1J 1Z4.

ABSTRACT
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. The 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.

No MeSH data available.


Related in: MedlinePlus