Regulation of B-cell commitment to plasma cells or to memory B cells

doi:10.1006/smim.1997.0080

Seminars in Immunology

Volume 9, Issue 4, August 1997, Pages 235-240

https://doi.org/10.1006/smim.1997.0080 Get rights and content

Abstract

During humoral immune responses, B-lymphocyte activation is followed by differentiation along either the plasma cell pathway or the memory B-cell pathway. Recent studies suggest that CD40–CD40 ligand, OX–OX40 ligand, a group of cytokines and intracellular transcriptional factors may all contribute to B-lymphocyte differentiation control.

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Cited by (90)

Modeling the kinetics of lymph node retention and exposure of a cargo protein delivered by biotin-functionalized nanoparticles
2023, Acta Biomaterialia
Generation of protective immunity through vaccination arises from the adaptive immune response developed primarily in the lymph nodes drained from the immunization site. Relative to the intramuscular route, subcutaneous administration allows for direct and rapid access to the lymphatics, but accumulation of soluble protein antigens within the lymph nodes is limited. Subunit vaccines also require immune stimulating adjuvants which may not accumulate in the same lymph nodes simultaneously with antigen. Herein we report the use of biotinylated poly (lactic-co-glycolic acid) nanoparticles (bNPs) to enhance delivery of a model protein antigen to the lymphatics. bNPs provide dual functionality as adjuvant and vehicle to localize antigens with stimulated immune cells in the same draining lymph node. Using streptavidin as a model antigen, which can be loaded directly onto the bNP surface, we evaluated the kinetics of lymph node occupancy and adaptive immune responses in wildtype C57BL/6 mice. Antigen exposure in vivo was significantly improved through surface loading onto bNPs, and we developed a working kinetic model to account for the retention of both particles and antigen in draining lymph nodes. We observed enhanced T cell responses and antigen-specific B cell response in vivo when antigen was delivered on the particle surface. This work highlights the advantage of combining intrinsic adjuvant and antigen loading in a single entity, and the utility of kinetic modeling in the understanding of particle-based vaccines.
Development of safe and effective subunit vaccines depends on effective formulations that render optimized exposure and colocalization of antigens and adjuvants. In this work, we utilize a nanoparticle system which features self-adjuvanting properties and allows for surface loading of recombinant protein antigens. Using in vivo imaging, we demonstrated prolonged co-localization of the antigen and adjuvant particles in draining lymph nodes and provided evidence of B cell activation for up to 21 days following subcutaneous injection. A pharmacokinetic model was developed as a step towards bridging the translational gap between particulate-based vaccines and observed outcomes. The results have implications for the rational design of particle-based vaccines.
A higher frequency of peripheral blood activated B cells in patients with non-traumatic osteonecrosis of the femoral head
2014, International Immunopharmacology
Citation Excerpt :
B cells are responsible for humoral responses mainly by producing a variety of autoantibodies, present antigens to activate T cells, and can secrete cytokines of IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ and TNF-α [10–20]. During functional development, B cells can be classified into different subsets, such as IgD + naïve, CD27 + memory, CD86 + and/or CD95 + activated B cells, and CD38 + plasma cells [10–16]. CD86 is a critical co-stimulatory molecule for B and T cell interaction, and the engagement of CD95 can trigger activated B cell apoptosis [14].
B cells play important roles in inflammatory diseases. This study was aimed at examining the frequency of different subsets of B cells in patients with non-traumatic osteonecrosis of the femoral head (NONFH).
The percentages of the different subsets of circulating B cells in 28 patients with steroid-related, alcohol-related, or idiopathic NONFH and 10 healthy controls (HC) were examined by flow cytometry. The concentrations of serum C-reactive protein (CRP), fibrinogen (FIB), immunoglobulins, cytokines and blood erythrocyte sedimentation rate (ESR) were measured.
In comparison with those in the HC, significantly higher percentages of CD27 −, CD86 +, CD95 +, and CD27 + CD95 +CD19 + but lower CD27 + CD19 + B cells were detected in the patients. The percentages of CD86 +, CD95 +, and CD27 + CD95 +CD19 + B cells in each group of the patients were significantly higher than those in the HC. The levels of serum IL-17A and IFN-γ in steroid group and serum TNF-α in alcoholic group were significantly higher than those in the HC. The percentages of CD86 + CD19 + B cells were positively associated with the degrees of femoral head collapse in both steroid and alcoholic groups of patients and the levels of serum TNF-α were positively associated with the degrees of femoral head collapse in the alcoholic NONFH patients.
These data suggest a higher frequency of CD86 + CD19 + activated B cells and elevated levels of serum TNF-α may be associated with the development of NONFH.
Peripheral B-cell activation and exhaustion markers in patients with ankylosing spondylitis
2013, Life Sciences
Citation Excerpt :
In addition, our data showed higher levels of CD95+ B cells in AS patients compared to HC. Since CD95 expression coincides with the acquisition of sensitivity to CD95− mediated apoptosis, this finding suggests that exhausted B cells might also play an important role in the pathogenesis of AS (Liu and Banchereau, 1997). Thus, the high expression of CD95 on B cells in AS patients might lead to enhanced spontaneous apoptosis in these patients.
Ankylosing spondylitis (AS) is an autoimmune disease and is associated with abnormal B cell function. However, the roles of different B cell subsets are less clear. This study aimed to examine the frequency of different subsets of B cells in AS patients following standard therapies.
Eighteen newly diagnosed AS patients and 10 healthy controls (HC) were recruited in this study. The expression of CD27, CD38, CD86, CD95 and IgD on CD19⁺ B cells was examined by flow cytometry. The disease activity was scored according to the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Serum levels of C-reactive protein (CRP), rheumatoid factor (RF), IgG, IgA and IgM, and the erythrocyte sedimentation rate (ESR) were measured.
The frequency of CD27⁺ B cells was decreased in AS patients compared with HC (p = 0.018), while CD86⁺ and CD27⁻CD95⁺ B cell subsets increased in AS patients (p < 0.001). Meanwhile, the frequencies of CD38⁺ and CD95⁺ B cell positively correlated with BASDAI (r = 0.6505, p = 0.0035; r = 0.6854, p = 0.0017, respectively), while CD38⁻CD86⁺ B cell negatively correlated with BASDAI (r = − 0.7329, p < 0.001). We also found that CD27⁻ and CD95⁺ B cell negatively correlated with RF levels (r = − 0.5141, p = 0.0290; r = − 0.4944, p = 0.0370, respectively), while CD27⁺ B cell positively correlated with IgG levels (p = 0.0148, r = 0.5640). Moreover, CD86⁺ and CD27⁻CD95⁺ B cell subsets increased following treatment with Meloxicam and Etanercept for one month (p < 0.001; p < 0.001).
These findings suggest that CD27⁻CD95⁺CD19⁺ and CD86⁺CD19⁺ B cells may be reasonable cellular targets for the therapeutic intervention of AS.
Defective regulatory B-cell compartment in patients with immune thrombocytopenia
2012, Blood
Citation Excerpt :
The underlying explanation for decreased memory B cells remains unknown, but it may be that because of continuous stimulation with platelet autoantigens, memory cells differentiate into plasma cells. Because naive B cells differentiate into either memory or plasma cells,39 another possibility may be that there is more plasma cell differentiation and therefore less memory cells in ITP patients. The disturbances in the B-cell compartment were particularly pronounced in our splenectomized ITP cohort, possibly caused by impaired B-cell differentiation resulting from loss of germinal centers of secondary lymphoid organs.33,34
B lymphocytes producing antiplatelet autoantibodies play a major role in autoimmune thrombocytopenia (ITP). However, certain B cells, including the human CD19⁺CD24^hiCD38^hi subpopulation, possess regulatory functions mediated partly by IL-10. In a cohort of chronic ITP patients with low platelet counts who consisted of patients off treatment, we found a lower frequency of CD19⁺CD24^hiCD38^hi in the peripheral compartment of nonsplenectomized patients (P = .03). IL-10 expression after activation was decreased in all ITP circulating CD19⁺ subpopulations (P < .03), and inhibition of monocyte TNF-α expression by activated B cells was reduced in patients with platelet numbers of < 50 × 10⁹ cells/L (P = .001), indicating that regulatory B cells of patients with ITP are functionally impaired in their ability to dampen monocyte activation. Interestingly, in nonsplenectomized patients whose platelet counts were elevated after treatment with thrombopoietic agents, the frequency of CD19⁺CD24^hiCD38^hi B cells was increased compared with those before treatment (P = .02). Altogether, these data indicate a compromised regulatory B-cell com-partment as an additional defect in immune regulation in patients with chronic ITP that may be restored in responders to thrombopoietic treatment.
Connection of BANK1, Tolerance, Regulatory B cells, and Apoptosis: Perspectives of a Reductionist Investigation
2021, Frontiers in Immunology
The immunological response toward botulinum toxin in individuals with facial rejuvenation
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Regular ArticleRegulation of B-cell commitment to plasma cells or to memory B cells

Abstract

Regular Article
Regulation of B-cell commitment to plasma cells or to memory B cells