Interleukin 10 (IL-10) upregulates functional high affinity IL-2 receptors on normal and leukemic B lymphocytes.

Fluckiger, Anne-Catherine; Garrone, Pierre; Durand, Isabelle; Galizzi, Jean‐Pierre; Banchereau, Jacques

doi:10.1084/jem.178.5.1473

Cited by 133 publications

(80 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6). The synergistic effect of IL-2 and IL-10 on growth and differentiation of human B cells has previously been attributed to the ability of IL-10 to increase expression of CD25 on CD40-activated B cells (29). Taken with our results, the B cells observed in this previous study to up-regulate CD25 were presumably memory B cells present in the population of total tonsillar B cells used (29).…”

Section: Discussionsupporting

confidence: 79%

“…The synergistic effect of IL-2 and IL-10 on growth and differentiation of human B cells has previously been attributed to the ability of IL-10 to increase expression of CD25 on CD40-activated B cells (29). Taken with our results, the B cells observed in this previous study to up-regulate CD25 were presumably memory B cells present in the population of total tonsillar B cells used (29). Our results predict that differentiation of naive B cells into memory B cells in vivo will alter the proliferative behavior of the resulting memory B cells in terms of time to enter division, magnitude of the response, and the growth factors capable of affecting this response.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Intrinsic Differences in the Proliferation of Naive and Memory Human B Cells as a Mechanism for Enhanced Secondary Immune Responses

Tangye

Avery

Deenick

et al. 2003

The Journal of Immunology

274

326

View full text Add to dashboard Cite

Humoral immune responses elicited after secondary exposure to immunizing Ag are characterized by robust and elevated reactivity of memory B cells that exceed those of naive B cells during the primary response. The mechanism underlying this difference in responsiveness of naive vs memory B cells remains unclear. We have quantitated the response of naive and memory human B cells after in vitro stimulation with T cell-derived stimuli. In response to stimulation with CD40 ligand alone or with IL-10, both IgM-expressing and Ig isotype-switched memory B cells entered their first division 20–30 h earlier than did naive B cells. In contrast, the time spent traversing subsequent divisions was similar. Consistent with previous studies, only memory cells differentiated to CD38+ blasts in a manner that increased with consecutive division number. These differentiated CD38+ B cells divided faster than did CD38− memory B cell blasts. Proliferation of CD40 ligand-stimulated naive B cells as well as both CD38+ and CD38− cells present in cultures of memory B cells was increased by IL-10. In contrast, IL-2 enhanced proliferation of CD38− and CD38+ memory B cell blasts, but not naive cells. Thus, memory B cells possess an intrinsic advantage over naive B cells in both the time to initiate a response and in the division-based rate of effector cell development. These differences help explain the accelerated Ab response exhibited by memory B cells after secondary challenge by an invading pathogen, a hallmark of immunological memory.

show abstract

Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Intrinsic Differences in the Proliferation of Naive and Memory Human B Cells as a Mechanism for Enhanced Secondary Immune Responses

Tangye

Avery

Deenick

et al. 2003

The Journal of Immunology

274

326

View full text Add to dashboard Cite

show abstract

“…Our findings have important biological implications, as the same stimuli that actively induce CSR, such as CD40L and IL-4, may enhance the in vivo accumulation of some elements of the CLL clone (52,54,56). Furthermore, ongoing CSR might introduce genomic instability.…”

Section: Cd40lmentioning

confidence: 97%

Ongoing In Vivo Immunoglobulin Class Switch DNA Recombination in Chronic Lymphocytic Leukemia B Cells

Cerutti

Zan

Kim

et al. 2002

The Journal of Immunology

View full text Add to dashboard Cite

Chronic lymphocytic leukemia (CLL) results from the expansion of malignant CD5+ B cells that usually express IgD and IgM. These leukemic cells can give rise in vivo to clonally related IgG+ or IgA+ elements. The requirements and modalities of this process remain elusive. Here we show that leukemic B cells from 14 of 20 CLLs contain the hallmarks of ongoing Ig class switch DNA recombination (CSR), including extrachromosomal switch circular DNAs and circle transcripts generated by direct Sμ→Sγ, Sμ→Sα, and Sμ→Sε as well as sequential Sγ→Sα and Sγ→Sε CSR. Similar CLL B cells express transcripts for activation-induced cytidine deaminase, a critical component of the CSR machinery, and contain germline IH-CH and mature VHDJH-CH transcripts encoded by multiple Cγ, Cα, and Cε genes. Ongoing CSR occurs in only a fraction of the CLL clone, as only small proportions of CD5+CD19+ cells express surface IgG or IgA and lack IgM and IgD. In vivo class-switching CLL B cells down-regulate switch circles and circle transcripts in vitro unless exposed to exogenous CD40 ligand and IL-4. In addition, CLL B cells that do not class switch in vivo activate the CSR machinery and secrete IgG, IgA, or IgE upon in vitro exposure to CD40 ligand and IL-4. These findings indicate that in CLL at least some members of the malignant clone actively differentiate in vivo along a pathway that induces CSR. They also suggest that this process is elicited by external stimuli, including CD40 ligand and IL-4, provided by bystander immune cells.

show abstract

“…Importantly, T cells in the microenvironment may induce CD25 upregulation in B-CLL cells by providing CD40 ligand and IL-10 as well as IL-2 [14,32]. IL-2 is then able to both induce proliferation and prevent apoptosis in the malignant cells and might 12 therefore play a central role in the balance between proliferation and apoptosis, which is determined in lymphoid tissues [40].…”

Section: Discussionmentioning

confidence: 99%

“…We and others have demonstrated that upregulation of CD25 in stimulated B-CLL cells results in the formation of functional high affinity receptors [13,14]. Importantly, IL-2 has demonstrated its potency to increase Immunglobulin secretion, cytokine production and upregulation of surface 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62...…”

mentioning

confidence: 99%

Antiapoptotic effect of interleukin-2 (IL-2) in B-CLL cells with low and high affinity IL-2 receptors

et al. 2010

View full text Add to dashboard Cite

Although B-CLL cells express the alpha chain of the IL-2 receptor CD25, little is known about the effect of IL-2 on apoptosis in B-CLL cells. We have shown previously that stimulation of B-CLL cells with a CpG-Oligonucleotide induces IL-2 high affinity receptors. In our current work, we analyzed the effect of IL-2 on apoptosis in resting B-CLL cells and in our model of activated B-CLL cells (CD25 high cells). IL-2 had modest antiapoptotic activity in resting B-CLL cells. In contrast, IL-2 was much more potent to prevent apoptosis in activated cells. Prevention of cell death was also associated with the maintenance of the mitochondrial membrane potential. While only limited regulation of apoptosis controlling proteins was observed in resting B-CLL cells, IL-2 had strong effects on MCL-1, Bcl-xl and survivin expression and inhibited Bax cleavage in CD25 high cells. Interestingly, expression of Bcl-2 was reduced. Addition of IL-2 to activated B-CLL cells caused rapid phosphorylation of Akt while IL-2 failed to significantly phosphorylate Akt in resting B-CLL cells. Pharmcological inhibition of Akt by LY294002 restored sensitivity of activated B-CLL cells to Fludarabine. IL-2 might be an important survival factor in activated B-CLL cells and contributes to disease progression by up-regulation of several critical antiapoptotic proteins.Response to Reviewers: Dear Reviewer, Thank you very much for your time and your efforts. We now provide a substantially shortened version of our manuscript (reduction from 3048 to 2475 words)and Figure 2 was deleted as requested. In addition, the number of citations was reduced from 49 to 41. We agree, that substantial shortening improved our manuscript.Thank you very much again. Annexin/PI staining was performed in 7 independent samples after culture for the indicated times with medium or IL-2 at 100U/ml. Cells were either cultured immediately after isolation (CD25 low) or after prestimulation with DSP30 and IL-2 for 24hours, followed by an overnight incubation with medium alone (CD25 high). B-CLL cells were cultured for 48 hours in medium alone or in the presence of DSP30 and IL-2 with or without Ly294002 (10µM) or Rapamycin (50ng/ml). Fludarabin (F) was added at 500 ng/ml as indicated. Apoptosis induction was calculated as described. Mean +/-SEM of 5 individual experiments are shown. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 A B

show abstract

Interleukin 10 (IL-10) upregulates functional high affinity IL-2 receptors on normal and leukemic B lymphocytes.

Cited by 133 publications

References 40 publications

Intrinsic Differences in the Proliferation of Naive and Memory Human B Cells as a Mechanism for Enhanced Secondary Immune Responses

Intrinsic Differences in the Proliferation of Naive and Memory Human B Cells as a Mechanism for Enhanced Secondary Immune Responses

Ongoing In Vivo Immunoglobulin Class Switch DNA Recombination in Chronic Lymphocytic Leukemia B Cells

Antiapoptotic effect of interleukin-2 (IL-2) in B-CLL cells with low and high affinity IL-2 receptors

Contact Info

Product

Resources

About