scholarly journals The Nod2 Agonist Muramyl Dipeptide Cooperates with the TLR4 Agonist Lipopolysaccharide to Enhance IgG2b Production in Mouse B Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Sang-Hoon Lee ◽  
Jong-Hwan Park ◽  
Seok-Rae Park
Keyword(s):  
B Cells ◽  
Cell Viability ◽  
B Cell ◽  
Muramyl Dipeptide ◽  
Combined Effect ◽  
Deficient Mouse ◽  
Cell Functions ◽  
Tlr4 Agonist ◽  
Cell Mitogen

Many studies have shown that Toll-like receptors (TLRs) and Nod-like receptors (NLRs) were expressed in B cells and their signaling affects B cell functions. Nonetheless, the roles played by these receptors in B cell antibody (Ab) production have not been completely elucidated. In the present study, we examined the effect of the Nod2 agonist muramyl dipeptide (MDP) in combination with the TLR4 agonist lipopolysaccharide (LPS), a well-known B cell mitogen, on B cell viability, proliferation, and activation, and Ab production by in vitro culture of purified mouse spleen resting B cells. MDP combined with LPS to reinforce B cell viability, proliferation, and activation. Moreover, MDP enhanced LPS-induced IgG2b production, germline γ2b transcript (GLTγ2b) expression, and surface IgG2b expression. In an experiment with Nod2- and TLR4-deficient mouse B cells, we observed that the combined effect of MDP and LPS is dependent on Nod2 and TLR4 receptors. Furthermore, the combined effect on B cell viability and IgG2b switching was not observed in Rip2-deficient mouse cells. Collectively, this study suggests that Nod2 signaling enhances TLR4-activated B cell proliferation, IgG2b switching, and IgG2b production.

scholarly journals Lymphocyte interleukin 2 production and responsiveness are altered in patients with primary myelodysplastic syndrome

Blood ◽  
1987 ◽  
Vol 70 (2) ◽  
pp. 494-500
Author(s):  
O Ayanlar-Batuman ◽  
J Shevitz ◽  
UC Traub ◽  
S Murphy ◽  
D Sajewski
Keyword(s):  
T Cells ◽  
B Cells ◽  
Myelodysplastic Syndrome ◽  
B Cell ◽  
Interleukin 2 ◽  
T Cell Proliferation ◽  
Cell Functions ◽  
Normal Limits ◽  
Stimulatory Capacity

Immunoregulatory T and B cell functions in 15 patients with primary myelodysplastic syndrome (MDS) were studied by measuring the proliferative and the stimulatory capacity of T and B cells, respectively, in autologous (auto) and allogeneic (allo) mixed lymphocyte reaction (MLR). T cell proliferation in the auto MLR was 25% of the control (P less than .02), whereas proliferation in the allo MLR was normal. When control T cells were stimulated by MDS B cells, their proliferative response was only 57% of the control (P less than .01). The mechanism responsible for these abnormalities was studied by determining the capacity of MDS and normal T cells to produce interleukin 2 (IL 2) and to generate IL 2 receptors (IL 2R) following stimulation with control and MDS B cells. In the auto MLR of MDS patients, only 3% +/- 2% of T cells developed IL 2R positivity, whereas in control cultures 12% +/- 2% of T cells were positive, as determined by immunofluorescence, using a monoclonal antibody (MoAb) directed against the IL 2R, and FACS analysis. When MDS T cells were stimulated by control B cells, IL 2R generation and the production of IL 2 were within normal limits. In contrast, when control T cells were stimulated by MDS B cells or control B cells, the MDS B cells induced production of only 26% of IL 2 as compared with control B cells. In parallel experiments, IL 2R generation in control T cells stimulated by either MDS or control B cells was similar. We conclude that in the primary MDS, T and B cell interactions are impaired. Although MDS T cells develop normal quantities of IL 2R and produce normal amounts of IL 2 when stimulated by control B cells, they are markedly impaired when stimulated by self B cells. Similarly, MDS B cells can induce IL 2R generation in control T cells but not in MDS T cells. Myelodysplastic B cells are also defective in inducing IL 2 production by normal T cells in an allo MLR. These in vitro abnormalities strongly suggest that generation of lymphocytes with immunoregulatory functions is impaired in patients with MDS.

scholarly journals Antibody Production and In Vitro Behavior of CD27-Defined B-Cell Subsets: Persistent Hepatitis C Virus Infection Changes the Rules

2006 ◽  
Vol 80 (8) ◽  
pp. 3923-3934 ◽  
Author(s):  
Vito Racanelli ◽  
Maria Antonia Frassanito ◽  
Patrizia Leone ◽  
Maria Galiano ◽  
Valli De Re ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Feedback Inhibition ◽  
Cell Subset ◽  
Functional Program ◽  
Cell Functions

ABSTRACT There is growing interest in the tendency of B cells to change their functional program in response to overwhelming antigen loading, perhaps by regulating specific parameters, such as efficiency of activation, proliferation rate, differentiation to antibody-secreting cells (ASC), and rate of cell death in culture. We show that individuals persistently infected with hepatitis C virus (HCV) carry high levels of circulating immunoglobulin G (IgG) and IgG-secreting cells (IgG-ASC). Thus, generalized polyclonal activation of B-cell functions may be supposed. While IgGs include virus-related and unrelated antibodies, IgG-ASC do not include HCV-specific plasma cells. Despite signs of widespread activation, B cells do not accumulate and memory B cells seem to be reduced in the blood of HCV-infected individuals. This apparent discrepancy may reflect the unconventional activation kinetics and functional responsiveness of the CD27+ B-cell subset in vitro. Following stimulation with T-cell-derived signals in the absence of B-cell receptor (BCR) engagement, CD27+ B cells do not expand but rapidly differentiate to secrete Ig and then undergo apoptosis. We propose that their enhanced sensitivity to BCR-independent noncognate T-cell help maintains a constant level of nonspecific serum antibodies and ASC and serves as a backup mechanism of feedback inhibition to prevent exaggerated B-cell responses that could be the cause of significant immunopathology.

scholarly journals Murine B-cell subpopulations responsive to T-dependent and T-independent antigens.

1976 ◽  
Vol 144 (2) ◽  
pp. 382-397 ◽  
Author(s):  
G K Lewis ◽  
R Ranken ◽  
D E Nitecki ◽  
J W Goodman
Keyword(s):  
B Cells ◽  
B Cell ◽  
Minor Component ◽  
Memory Cell ◽  
Keyhole Limpet Hemocyanin ◽  
The Other ◽  
Other Hand ◽  
Cell Mitogen ◽  
A Minor

Strain A/J mice made secondary indirect plaque-forming cell (PFC) responses to azobenzenearsonate (ABA) conjugates of giant keyhole limpet hemocyanin (KLH), a thymic-dependent antigen, but not to conjugates of Ficoll, a T-independent antigen. ABA-Ficoll was also unable to elicit a response in animals primed with ABA-KLH, which have an expanded anti-ABA memory cell pool. On the other hand, ABA-Ficoll rendered mice unresponsive to ABA-KLH when administered before priming or boosting with the T-dependent immunogen. Hence, the T-independent antigen was able to tolerize but unable to trigger B-memory cells responsive to the T-dependent antigen. A/J mice immunized with dinitrophenyl conjugates of Ficoll or bovine IgG (BGG) made vigorous IgM and IgG PFC responses. PFC responses to ABA-KLH and 2,4-dinitrophenyl (DNP)-BGG were abrogated by depleting mice of C3 with cobra venom factor, whereas the IgM and IgG PFC responses to DNP-Ficoll were unaffected. B lymphocytes were fractionated on the basis of receptors for C3 and the subpopulations were assayed for in vitro PFC responses to DNP-Ficoll. Very little response was obtained from complement receptor lymphocyte [CRL(+)] B cells, whereas CRL(-) cells were more responsive than unfractionated B cells. Both populations responded to a polyclonal B-cell mitogen (lipopolysaccharide). On the other hand, the in vitro PFC response to a T-dependent antigen (sheep erythrocytes) correlated with the presence of CRL(+) B cells in the cultures. However, a minor component of this response, sensitive to anti-Thy-1 serum, was made by CRL(-) B cells, indicating the existence of subpopulations of T-dependent B cells with different signalling requirements. The results suggest that most B cells responsive to T-dependent antigens possess receptors for C3 and that C3 plays an obligatory role in the response of these cells. A distinct subpopulation of B cells which lack C3 receptors respond to T-independent antigens. The precursors of PFC for the ABA epitope reside largely or exclusively in the CRL(+) compartment in A/J mice, whereas precursors for the DNP determinant are found in both compartments.

scholarly journals Immunologic properties of bacterial lipopolysaccharide (LPS). III. Genetic linkage between the in vitro mitogenic and in vivo adjuvant properties of LPS.

1976 ◽  
Vol 143 (1) ◽  
pp. 143-150 ◽  
Author(s):  
B J Skidmore ◽  
J M Chiller ◽  
W O Weigle ◽  
R Riblet ◽  
J Watson
Keyword(s):  
B Cells ◽  
B Cell ◽  
Tolerance Induction ◽  
Backcross Progeny ◽  
Bacterial Lipopolysaccharide ◽  
Adjuvant Activity ◽  
F1 Hybrid ◽  
Cell Mitogen

The mechanism was investigated underlying the activity of bacterial lipopolysaccharide (LPS) as an adjuvant of antibody formation as assessed by its capacity to modulate the induction of tolerance in mice to the antigen human Ig G (HGG) into a state of immunity to HGG. The adjuvant activity of LPS was found to be closely correlated with its ability to function as a B-cell mitogen. This correlation was revealed by an analysis of the genetic control of the mitogenic and adjuvant properties of LPS utilizing the refractory state inherent in the C3H/HeJ mouse strain to these activities of LPS. Thus, mice that were the progeny of a backcross between the nonresponder C3H/JeJ parent and the responder (C3H/HeJ X CWB) F1 hybrid were individually typed for responsiveness to LPS, as an adjuvant and as a B-cell mitogen. It was found that LPS interfered with tolerance induction to HGG in vivo only in those backcross progeny whose spleen cells were also capable of responding mitogenically to LPS in vitro, demonstrating that the adjuvant and B-cell mitogenic properties of LPS are genetically linked. In contrast, these properties were observed to segregate independently from either H-2 or heavy chain allotype loci, and were not sex linked. These results are compatible with the concepts that, in this system, (a) the cellular site of action of LPS as an adjuvant is confined to B cells, and (b) the subcellular mode of action of LPS as an adjuvant may involve the delivery of a "signal" to B cells which is a stimulus for mitogenesis.

scholarly journals Targeting human langerin promotes HIV-1 specific humoral immune responses

2021 ◽  
Vol 17 (7) ◽  
pp. e1009749
Author(s):  
Jérôme Kervevan ◽  
Aurélie Bouteau ◽  
Juliane S. Lanza ◽  
Adele Hammoudi ◽  
Sandra Zurawski ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Serum Levels ◽  
Target Antigen ◽  
Humoral Immune ◽  
Cell Functions ◽  
Tfh Cells ◽  
Specific Igg ◽  
Hiv 1

The main avenue for the development of an HIV-1 vaccine remains the induction of protective antibodies. A rationale approach is to target antigen to specific receptors on dendritic cells (DC) via fused monoclonal antibodies (mAb). In mouse and non-human primate models, targeting of skin Langerhans cells (LC) with anti-Langerin mAbs fused with HIV-1 Gag antigen drives antigen-specific humoral responses. The development of these immunization strategies in humans requires a better understanding of early immune events driven by human LC. We therefore produced anti-Langerin mAbs fused with the HIV-1 gp140z Envelope (αLC.Env). First, we show that primary skin human LC and in vitro differentiated LC induce differentiation and expansion of naïve CD4+ T cells into T follicular helper (Tfh) cells. Second, when human LC are pre-treated with αLC.Env, differentiated Tfh cells significantly promote the production of specific IgG by B cells. Strikingly, HIV-Env-specific Ig are secreted by HIV-specific memory B cells. Consistently, we found that receptors and cytokines involved in Tfh differentiation and B cell functions are upregulated by LC during their maturation and after targeting Langerin. Finally, we show that subcutaneous immunization of mice by αLC.Env induces germinal center (GC) reaction in draining lymph nodes with higher numbers of Tfh cells, Env-specific B cells, as well as specific IgG serum levels compared to mice immunized with the non-targeting Env antigen. Altogether, we provide evidence that human LC properly targeted may be licensed to efficiently induce Tfh cell and B cell responses in GC.

scholarly journals MECHANISM OF THYMUS-INDEPENDENT IMMUNOCYTE TRIGGERING

1974 ◽  
Vol 139 (1) ◽  
pp. 74-92 ◽  
Author(s):  
Antonio Coutinho ◽  
Eva Gronowicz ◽  
Wesley W. Bullock ◽  
Göran Möller
Keyword(s):  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Antigenic Determinants ◽  
High Avidity ◽  
Polyclonal Activation ◽  
Low Concentrations ◽  
Specific Receptors ◽  
Cell Mitogen

The present experiments were performed in order to analyze the mechanism by which thymus-independent antigens (nonspecific B-cell mitogens) can induce specific immune responses to antigenic determinants present on the same molecule. The hapten NNP was coupled to the B-cell mitogen, lipopolysaccharide (LPS). The conjugate retained full mitogenic activity and bound specifically to NNP-reactive cells. NNP-LPS activated polyclonal as well as specific anti-NNP antibody synthesis, but the optimal concentrations for induction of specific anti-NNP cells were several orders of magnitude lower than the concentrations required for polyclonal activation. These low concentrations failed to activate nonspecific cells, but they induced specific thymus-independent responses of high-avidity NNP-specific cells with the typical kinetics of antigenic responses in vitro. Furthermore, hapten-specific cells were paralyzed by NNP-LPS concentrations that were optimal for induction of polyclonal activation. Specific activation and paralysis could be abolished by free hapten indicating that selective binding of NNP-LPS to hapten-specific cells was responsible for the specificity of the response. However, the triggering signal lacked specificity, since high-avidity specific anti-NNP cells could still be activated by stimulating concentrations of NNP-LPS in the presence of free hapten, even though the Ig receptor combining sites were presumably occupied by NNP. The findings show that B cells with specific Ig receptors for the antigenic determinants on mitogen molecules preferentially bind these molecules and become activated at concentrations still unsufficient to trigger other B cells that lack specific receptors. It is suggested that activation for primary IgM responses in B cells is the result of "one nonspecific signal." This nonspecific signal is provided by the mitogenic properties of some antigens (highly thymus independent or, alternatively, by nonspecific T-cell factors (for highly T cell-dependent antigens), or both, and the surface structures responsible for triggering are not the Ig receptors. The specific Ig receptors only act as passive focusing devices for nonspecific stimuli, entitling the cell to be selectively activated, even though both the signal and the receptors for the triggering are nonspecific.

Antibody-Deficiency and Acute Nephritic Syndrome in a Patient with Homozygous Disruption of the CD81 Gene

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 83-83
Author(s):  
Menno C van Zelm ◽  
Julie Smet ◽  
Françoise Mascart ◽  
Brigitte Adams ◽  
Liliane Schandené ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Motor Development ◽  
Transmembrane Domain ◽  
Pcr Analysis ◽  
Expression Levels ◽  
Cell Functions ◽  
Nephritic Syndrome ◽  
Acute Nephritic Syndrome

Abstract The tetraspan molecule CD81 is widely expressed on immune cells, such as B-, T-, NK-lymphocytes, monocytes and eosinophils, but also on most stromal and epithelial cells and on hepatocytes. In B-cells it is a member of the CD19 complex (CD19, CD21, CD81, CD225), which is required for signaling together with the B-cell antigen receptor upon antigen recognition. Its functions on other cells are unclear, but murine studies show an antiproliferative role for CD81. On hepatocytes, two different epitopes of CD81 act as a co-receptor for Hepatitis C virus and for Plasmodium infection. We evaluated a 4-year-old girl from consanguineous parents of Moroccan decent. She presented with recurrent infections and an acute nephrotic syndrome: >50% of glomeruli were affected due to focal mesangial hypercellularity. She showed poor weight gain (below 3rd percentile), but normal motor development. Her spleen and liver were enlarged, but function normally. Measurements of retina epithelium and CNS showed no signs of hypercellularity. Although serum IgG levels were strongly decreased (2.4 g/L) and IgM and IgA concentrations low within normal range, she tested positive for anti-platelet antibodies. Flow cytometric immunophenotyping of blood showed normal distribution and absolute numbers of granulocyte, monocyte and lymphocyte subsets; however, no CD19 expression was detected on the patient’s B-cells, whereas CD21 expression levels were normal. The patient carried no mutations in the CD19 and IFITM1 (CD225) genes. Additional immunophenotyping showed that all cells lacked CD81 expression. Sequencing of the CD81 gene showed a homozygous G>A substitution immediately downstream of exon 6 (c.561+1G>A). Spectratyping and quantitative PCR analysis showed clearly reduced total CD81 mRNA expression levels. Nearly all CD81 transcripts contained 13 additional nucleotides downstream of exon 6. This insertion results in a frame-shift and a premature stop (p.Glu188MetfsX13). The hypothetical protein lacks the fourth transmembrane domain. Similar to previously described CD19-deficient patients, our patient had reduced numbers CD5+ B-cells and Ig class switched and non-switched CD27+ memory-B cells. Whereas Vh-Cα and Vh-Cγ transcripts from Ig switched cells contained somatic hypermutations, the response of the patient’s B cells to in vitro stimulation through the B-cell receptor was impaired. The antibody response to rabies, tetanus and pneumococcal vaccinations is currently under investigation, as well as the potential impact of CD81 deficiency on the antigen-specific Th1 and Th2 cytokine production. In conclusion, the here presented CD81 deficiency is a new primary immunodeficiency, which leads to disruption of the CD19 complex and consequent hypogammaglobulinemia comparable to the CD19 deficiency. However, due to the broad tissue distribution, the clinical phenotype is not restricted to the B-cell system. Other organs are affected as well, most likely due to excessive proliferation and hypercellularity, with acute nephritic syndrome as dominant clinical problem. Currently, in vitro studies are being performed to identify whether the CD81 defect directly results in impaired B-cell and T-cell functions and abnormal proliferation of kidney and liver cells.

scholarly journals Lymphocyte interleukin 2 production and responsiveness are altered in patients with primary myelodysplastic syndrome

Blood ◽  
1987 ◽  
Vol 70 (2) ◽  
pp. 494-500 ◽  
Author(s):  
O Ayanlar-Batuman ◽  
J Shevitz ◽  
UC Traub ◽  
S Murphy ◽  
D Sajewski
Keyword(s):  
T Cells ◽  
B Cells ◽  
Myelodysplastic Syndrome ◽  
B Cell ◽  
Interleukin 2 ◽  
T Cell Proliferation ◽  
Cell Functions ◽  
Normal Limits ◽  
Stimulatory Capacity

Abstract Immunoregulatory T and B cell functions in 15 patients with primary myelodysplastic syndrome (MDS) were studied by measuring the proliferative and the stimulatory capacity of T and B cells, respectively, in autologous (auto) and allogeneic (allo) mixed lymphocyte reaction (MLR). T cell proliferation in the auto MLR was 25% of the control (P less than .02), whereas proliferation in the allo MLR was normal. When control T cells were stimulated by MDS B cells, their proliferative response was only 57% of the control (P less than .01). The mechanism responsible for these abnormalities was studied by determining the capacity of MDS and normal T cells to produce interleukin 2 (IL 2) and to generate IL 2 receptors (IL 2R) following stimulation with control and MDS B cells. In the auto MLR of MDS patients, only 3% +/- 2% of T cells developed IL 2R positivity, whereas in control cultures 12% +/- 2% of T cells were positive, as determined by immunofluorescence, using a monoclonal antibody (MoAb) directed against the IL 2R, and FACS analysis. When MDS T cells were stimulated by control B cells, IL 2R generation and the production of IL 2 were within normal limits. In contrast, when control T cells were stimulated by MDS B cells or control B cells, the MDS B cells induced production of only 26% of IL 2 as compared with control B cells. In parallel experiments, IL 2R generation in control T cells stimulated by either MDS or control B cells was similar. We conclude that in the primary MDS, T and B cell interactions are impaired. Although MDS T cells develop normal quantities of IL 2R and produce normal amounts of IL 2 when stimulated by control B cells, they are markedly impaired when stimulated by self B cells. Similarly, MDS B cells can induce IL 2R generation in control T cells but not in MDS T cells. Myelodysplastic B cells are also defective in inducing IL 2 production by normal T cells in an allo MLR. These in vitro abnormalities strongly suggest that generation of lymphocytes with immunoregulatory functions is impaired in patients with MDS.

scholarly journals CXCR4 promotes B cell viability by the cooperation of nuclear factor (erythroid-derived 2)-like 2 and hypoxia-inducible factor-1α under hypoxic conditions

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Ju-Won Jang ◽  
Pham Xuan Thuy ◽  
Jae-Wook Lee ◽  
Eun-Yi Moon
Keyword(s):  
B Cells ◽  
Cell Viability ◽  
B Cell ◽  
Hypoxia Inducible Factor ◽  
Gene Promoter ◽  
Hypoxic Condition ◽  
Cxcr4 Expression ◽  
Nuclear Factor ◽  
Cell Functions ◽  
Hypoxic Conditions

AbstractB cells that interact with T cells play a role in regulating the defense function by producing antibodies and inflammatory cytokines. C-X-C chemokine receptor type 4 (CXCR4) is a specific receptor for stromal cell-derived factor 1 (SDF-1) that controls various B cell functions. Here, we investigated whether CXCR4 regulates B cell viability by inducing hypoxia-inducible factor (HIF)-1α and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) under a hypoxic condition in WiL2-NS human B cells. Nrf2 and CXCR4 expressions increased significantly when WiL2-NS cells were incubated under a hypoxic condition. Interfering with CXCR4 expression using CXCR4-siRNA inhibited cell viability. CXCR4 expression also decreased after treatment with a HIF inhibitor under the hypoxic condition, leading to inhibited cell viability. Increased reactive oxygen species (ROS) levels and the expression of HIF-1α and Nrf2 decreased under the hypoxic condition following incubation with N-acetylcysteine, a ROS scavenger, which was associated with a decrease in CXCR4 expression. CXCR4 expression was augmented by overexpressing Nrf2 after transfecting the pcDNA3.1-Nrf2 plasmid. CXCR4 expression decreased and HIF-1α accumulation decreased when Nrf2 was inhibited by doxycycline in tet-shNrf2-expressed stable cells. Nrf2 or HIF-1α bound from −718 to −561 of the CXCR4 gene promoter as judged by a chromatin immunoprecipitation assay. Taken together, these data show that B cell viability under a hypoxic condition could be regulated by CXCR4 expression through binding of HIF-1α and Nrf2 to the CXCR4 gene promoter cooperatively. These results suggest that CXCR4 could be an additional therapeutic target to control B cells with roles at disease sites under hypoxic conditions.

Ligation of tumour-produced mucins to CD22 dramatically impairs splenic marginal zone B-cells

2009 ◽  
Vol 417 (3) ◽  
pp. 673-683 ◽  
Author(s):  
Munetoyo Toda ◽  
Risa Hisano ◽  
Hajime Yurugi ◽  
Kaoru Akita ◽  
Kouji Maruyama ◽  
...  
Keyword(s):  
Sialic Acid ◽  
B Cells ◽  
B Cell ◽  
Marginal Zone ◽  
Cell Signalling ◽  
Negative Regulator ◽  
Mammary Adenocarcinoma ◽  
Marginal Zone B Cells ◽  
Tumour Bearing

CD22 [Siglec-2 (sialic acid-binding, immunoglobulin-like lectin-2)], a negative regulator of B-cell signalling, binds to α2,6- sialic acid-linked glycoconjugates, including a sialyl-Tn antigen that is one of the typical tumour-associated carbohydrate antigens expressed on various mucins. Many epithelial tumours secrete mucins into tissues and/or the bloodstream. Mouse mammary adenocarcinoma cells, TA3-Ha, produce a mucin named epiglycanin, but a subline of them, TA3-St, does not. Epiglycanin binds to CD22 and inhibits B-cell signalling in vitro. The in vivo effect of mucins in the tumour-bearing state was investigated using these cell lines. It should be noted that splenic MZ (marginal zone) B-cells were dramatically reduced in the mice bearing TA3-Ha cells but not in those bearing TA3-St cells, this being consistent with the finding that the thymus-independent response was reduced in these mice. When the mucins were administered to normal mice, a portion of them was detected in the splenic MZ associated with the MZ B-cells. Furthermore, administration of mucins to normal mice clearly reduced the splenic MZ B-cells, similar to tumour-bearing mice. These results indicate that mucins in the bloodstream interacted with CD22, which led to impairment of the splenic MZ B-cells in the tumour-bearing state.

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