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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

Phenotypes of PPBL B cells following low CD154 interaction. CD19, CD27, IgD, and IgM expressions were evaluated by flow cytometry on B cells receiving a low level of CD154 interaction (shown in Figure 2), at days 8 to 9 (9 d) or 13 to 14 (14 d), as indicated. (a) Phenotypic profiles are shown for one control (C-01) and one PPBL sample (8010). (b) The frequencies of cells in the three control samples and the 6 PPBL samples are shown for the main subsets of CD19+CD27−, CD19+CD27+, IgM−IgD−, and IgM+IgD− cells, as illustrated in. (a) Data is presented as mean ± SD.
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fig3: Phenotypes of PPBL B cells following low CD154 interaction. CD19, CD27, IgD, and IgM expressions were evaluated by flow cytometry on B cells receiving a low level of CD154 interaction (shown in Figure 2), at days 8 to 9 (9 d) or 13 to 14 (14 d), as indicated. (a) Phenotypic profiles are shown for one control (C-01) and one PPBL sample (8010). (b) The frequencies of cells in the three control samples and the 6 PPBL samples are shown for the main subsets of CD19+CD27−, CD19+CD27+, IgM−IgD−, and IgM+IgD− cells, as illustrated in. (a) Data is presented as mean ± SD.

Mentions: The phenotypes of PPBL B cells following low CD40 stimulation were monitored for CD19, CD27, IgM, and IgD expression on days 9 and 14. Phenotypic profiles for one representative PPBL sample and an example of control B cells are presented below (Figure 3(a)). The frequencies for CD19+CD27−, CD19+CD27+, IgM−IgD−, and IgM+IgD− cells are shown as the mean values for all PPBL samples (n = 6) and the three controls (Figure 3(b)). Phenotypic evolution of the CD19+ B cells, similar in all PPBL samples, differed from that of control B cells by showing a higher frequency of CD27+ and IgM+IgD− cells (Figures 3(a) and 3(b)). In all samples, two main phenotypes, corresponding to CD19+CD27− and CD19+CD27+ cells, were observed during days 9 through 14. Based upon CD27 expression, the evolution of B cells from PPBL patients, following low CD40 stimulation, appeared similar to that of B cells from healthy controls. At rest, 81 to 96% of PPBL B cells were IgDloIgM+ (Figure 1), a phenotype similar to that of normal marginal zone B cells [11, 34]. Following CD40 stimulation, surface IgD almost vanished in all PPBL B cell samples (Figures 3(a) and 3(b)). Additionally, the frequency of total IgM+ B cells decreased in controls, from 88 to 95% (day 0) to less than 10% of CD19+ cells (day 14), while remaining at 57% ± 15% in PPBL samples. Overall, these results indicate that the response of PPBL B cells to CD40 stimulation leads to phenotype changes that are quite similar to those observed in normal B cell populations but that remains biased towards growth of IgM+ B cell subsets.


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)

Phenotypes of PPBL B cells following low CD154 interaction. CD19, CD27, IgD, and IgM expressions were evaluated by flow cytometry on B cells receiving a low level of CD154 interaction (shown in Figure 2), at days 8 to 9 (9 d) or 13 to 14 (14 d), as indicated. (a) Phenotypic profiles are shown for one control (C-01) and one PPBL sample (8010). (b) The frequencies of cells in the three control samples and the 6 PPBL samples are shown for the main subsets of CD19+CD27−, CD19+CD27+, IgM−IgD−, and IgM+IgD− cells, as illustrated in. (a) Data is presented as mean ± SD.
© Copyright Policy
Related In: Results  -  Collection

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

fig3: Phenotypes of PPBL B cells following low CD154 interaction. CD19, CD27, IgD, and IgM expressions were evaluated by flow cytometry on B cells receiving a low level of CD154 interaction (shown in Figure 2), at days 8 to 9 (9 d) or 13 to 14 (14 d), as indicated. (a) Phenotypic profiles are shown for one control (C-01) and one PPBL sample (8010). (b) The frequencies of cells in the three control samples and the 6 PPBL samples are shown for the main subsets of CD19+CD27−, CD19+CD27+, IgM−IgD−, and IgM+IgD− cells, as illustrated in. (a) Data is presented as mean ± SD.
Mentions: The phenotypes of PPBL B cells following low CD40 stimulation were monitored for CD19, CD27, IgM, and IgD expression on days 9 and 14. Phenotypic profiles for one representative PPBL sample and an example of control B cells are presented below (Figure 3(a)). The frequencies for CD19+CD27−, CD19+CD27+, IgM−IgD−, and IgM+IgD− cells are shown as the mean values for all PPBL samples (n = 6) and the three controls (Figure 3(b)). Phenotypic evolution of the CD19+ B cells, similar in all PPBL samples, differed from that of control B cells by showing a higher frequency of CD27+ and IgM+IgD− cells (Figures 3(a) and 3(b)). In all samples, two main phenotypes, corresponding to CD19+CD27− and CD19+CD27+ cells, were observed during days 9 through 14. Based upon CD27 expression, the evolution of B cells from PPBL patients, following low CD40 stimulation, appeared similar to that of B cells from healthy controls. At rest, 81 to 96% of PPBL B cells were IgDloIgM+ (Figure 1), a phenotype similar to that of normal marginal zone B cells [11, 34]. Following CD40 stimulation, surface IgD almost vanished in all PPBL B cell samples (Figures 3(a) and 3(b)). Additionally, the frequency of total IgM+ B cells decreased in controls, from 88 to 95% (day 0) to less than 10% of CD19+ cells (day 14), while remaining at 57% ± 15% in PPBL samples. Overall, these results indicate that the response of PPBL B cells to CD40 stimulation leads to phenotype changes that are quite similar to those observed in normal B cell populations but that remains biased towards growth of IgM+ B cell subsets.

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