**4. Discussion**

In the spleen, there are complex processes of differentiation, selection of B lymphocytes, and replenishment of the pool of recirculating B lymphocytes and the pool of BMZ and B1 cells.

Coexpression of CD38 and CD25 can be observed within the B cell population of the marginal zone of the spleen. B cells of the marginal zone (BMZ) originate from a pool of recycled B lymphocytes that have returned to the marginal zone of the spleen. Phenotypically, these cells are more similar to B2 cells than to B1 cells. They come from the same bone marrow precursor cells.

These cells have specific morphological features: IgM molecules are expressed on their membrane, but there are no IgD molecules [49]. IgM is expressed more strongly than on B2 cells. For BMZ, high expression of CD21 is characteristic, which allows them to successfully bind TH2 antigens (T cell-independent type 2 antigens), presented in particular on encapsulated bacteria [50, 51]. The molecules of СD69, СD25, and СD38 in a small amount of СD23 are expressed on BMZ. B lymphocytes with this phenotype are also found in other lymphoid tissues, but only the marginal zone of the spleen accumulates the largest number of these cells in the body.

Information on antigens of BMZ is obtained by "shuttle" migration to lymphoid follicles and back. When responding to antigens, the BMZ cells differentiate into short-lived antibody-forming cells. Due to the strong expression of MHC-11 molecules and costimulatory molecules, BMZ cells have a pronounced ability to interact with T-helper cells.

B1 lymphocytes are small group of B cells, found in humans and mice. CD5+ population differs from B2 cells by their phenotype, anatomical localization, self-healing ability, and the production of natural antibodies, includes two subpopulations: B1a and B1b [32, 33]. B1 lymphocytes develop in the fetal liver from progenitor cells.

The predecessors of B1a lymphocytes in ontogenesis appear before other subpopulations and migrate from the embryonic hematopoietic tissues (fetal liver and omentum) to the abdominal and pleural cavities as early as the embryonic period. B1b lymphocytes also originate from fetal precursors, but their pool in adults can be partially replenished by the bone marrow and migrate to the serous cavities during the embryonic period where they exist throughout the life of the organism [34, 35]. Thus, during life, the B1 lymphocyte pool is maintained by the activity of progenitor cells through their very slow proliferation. B1 cells are characterized by an "activated phenotype" which is manifested in the expression on their surface of costimulatory molecules CD80 and CD86. This property provides the ability of B1 lymphocytes to function as antigen-presenting cells. Subpopulations of B1 lymphocytes are similar, but subpopulation of В1b is characterized by the absence of CD5 expression [36].

The data obtained show a disruption in the composition of B cell subpopulations. Most peripheral blood B cells showed weak levels of CD21 (low) antigen expression, marked presence of a pronounced amount of CD2+ B cells, and cases of clonal B cells. This probably reduces the function of antibody formation in the case of the realization of the main path of development of antibody producers in response to thymus-dependent antigens.

The antibodies produced by B1 lymphocytes are almost exclusively IgM. The response of B1 cells is predominantly thymus-independent [37]. IgM plays an important role in the induction of apoptosis of tumor cells [38–40]. Approximately half of the serum IgM is secreted by B1 cells. A small number of B1 lymphocytes, mainly cells secreting antibodies, are detected in the spleen, where they account for up to 5% of the number of B cells.

In the works which were devoted to the study of the function of the spleen and performed on animals, it has been shown that after splenectomy in the serum, the IgM level and the phagocytic activity of neutrophilic granulocytes decreased. However, if the spleen is reimplanted, the concentration of IgM is increased [52].

In a clinical study conducted at our research center, the levels of the main IgG, IgM, and IgA immunoglobulin classes were studied in patients with gastric cancer who underwent a standard operation in the volume of gastrectomy and lymphadenectomy with splenectomy [53].

The level of immunoglobulins was determined by the method of radial immunodiffusion in Mancini with the use of test systems produced by the SPC Medical Immunology (Russia). The level of immunoglobulins A, G, and M in serum in patients without splenectomy, from 14 days after the operation, was slightly elevated and decreased to the initial value by 3 months (**Figure 6a**).

The level of all investigated immunoglobulins in the blood serum in patients with splenectomy before the operation was within the physiological norm. The content of IgA initially and for the entire monitoring period was within physiological values. The authors found that the levels of immunoglobulins G and M in

**145**

*Splenectomy in Gastric Cancer: Influence of B Lymphocytes*

antigens may lead to decrease in antibody production.

*serum in patients in the dynamics in the postoperative period with a splenectomy.*

probably have an alternative TH2 response to pathogens.

patients with gastric cancer who underwent surgical treatment with splenectomy were reduced almost twofold from the baseline, from the 14th day to the 3rd month

*(a) The level of immunoglobulin IgA, IgG, and IgM in the blood serum in patients in the dynamics in the postoperative period without splenectomy and (b) the level of immunoglobulin IgA, IgG, and IgM in the blood* 

This fact agrees with the data obtained by our study. Change in the immunological repertoire of B2 cell antigens, weak expression of the CD21 membrane antigen, and a significant amount of CD23+ cells in the case of realization of the main pathway of development of antibody producers in response to thymus-dependent

Among peripheral blood lymphocytes, the presence of CD19+CD5+ B cells (B1a cells), some of which express the activation antigens CD38 and CD23, is found; a small part of CD5+ B cells is CD25+CD38−. Given the membrane immunophenotype circulating in the peripheral blood of B cells, patients with gastric cancer

In the group of patients after surgical intervention in the volume of gastrectomy with standard D2 lymphodissection and splenectomy, the relative total number of CD19+ B lymphocytes and the number of CD19+CD21+ B cells decreased (the differences are close to reliable) compared to preoperative values. In the group of patients with standard D2 lymphodissection and splenectomy, the percentage of CD5+ B lymphocytes significantly increased from 12.9 to 21.8%, after the operation. Given data on B1 and BMZ populations, this can lead to a weakening of both general and antitumor immunity. Since maintaining the population B1 population is

very slow, and the renewal of the BMZ pool is possible only in the spleen.

Immunosuppression in patients who underwent surgery (including splenectomy) develops as a result of a disruption in the composition of B cell link. Disorders of the immune response primarily affect the population of B1a lymphocytes, which provides a response to thymus-independent antigens of the second type. Patients in the experimental group may experience decreased production of antibodies, includ-

ing IgM, which plays an important role in inducing apoptosis of tumor cells.

We hereby inform you that there is no conflict of interest**.**

*DOI: http://dx.doi.org/10.5772/intechopen.80075*

of **Figure 6b**.

**Figure 6.**

**5. Conclusion**

**Conflict of interest**

*Splenectomy in Gastric Cancer: Influence of B Lymphocytes DOI: http://dx.doi.org/10.5772/intechopen.80075*

#### **Figure 6.**

*Normal and Malignant B-Cell*

with T-helper cells.

progenitor cells.

expression [36].

response to thymus-dependent antigens.

up to 5% of the number of B cells.

enectomy with splenectomy [53].

Information on antigens of BMZ is obtained by "shuttle" migration to lymphoid follicles and back. When responding to antigens, the BMZ cells differentiate into short-lived antibody-forming cells. Due to the strong expression of MHC-11 molecules and costimulatory molecules, BMZ cells have a pronounced ability to interact

B1 lymphocytes are small group of B cells, found in humans and mice. CD5+ population differs from B2 cells by their phenotype, anatomical localization, self-healing ability, and the production of natural antibodies, includes two subpopulations: B1a and B1b [32, 33]. B1 lymphocytes develop in the fetal liver from

The predecessors of B1a lymphocytes in ontogenesis appear before other subpopulations and migrate from the embryonic hematopoietic tissues (fetal liver and omentum) to the abdominal and pleural cavities as early as the embryonic period. B1b lymphocytes also originate from fetal precursors, but their pool in adults can be partially replenished by the bone marrow and migrate to the serous cavities during the embryonic period where they exist throughout the life of the organism [34, 35]. Thus, during life, the B1 lymphocyte pool is maintained by the activity of progenitor cells through their very slow proliferation. B1 cells are characterized by an "activated phenotype" which is manifested in the expression on their surface of costimulatory molecules CD80 and CD86. This property provides the ability of B1 lymphocytes to function as antigen-presenting cells. Subpopulations of B1 lymphocytes are similar, but subpopulation of В1b is characterized by the absence of CD5

The data obtained show a disruption in the composition of B cell subpopulations. Most peripheral blood B cells showed weak levels of CD21 (low) antigen expression, marked presence of a pronounced amount of CD2+ B cells, and cases of clonal B cells. This probably reduces the function of antibody formation in the case of the realization of the main path of development of antibody producers in

The antibodies produced by B1 lymphocytes are almost exclusively IgM. The response of B1 cells is predominantly thymus-independent [37]. IgM plays an important role in the induction of apoptosis of tumor cells [38–40]. Approximately half of the serum IgM is secreted by B1 cells. A small number of B1 lymphocytes, mainly cells secreting antibodies, are detected in the spleen, where they account for

In the works which were devoted to the study of the function of the spleen and performed on animals, it has been shown that after splenectomy in the serum, the IgM level and the phagocytic activity of neutrophilic granulocytes decreased. However, if the spleen is reimplanted, the concentration of IgM is increased [52]. In a clinical study conducted at our research center, the levels of the main IgG, IgM, and IgA immunoglobulin classes were studied in patients with gastric cancer who underwent a standard operation in the volume of gastrectomy and lymphad-

The level of immunoglobulins was determined by the method of radial immunodiffusion in Mancini with the use of test systems produced by the SPC Medical Immunology (Russia). The level of immunoglobulins A, G, and M in serum in patients without splenectomy, from 14 days after the operation, was slightly

The level of all investigated immunoglobulins in the blood serum in patients with splenectomy before the operation was within the physiological norm. The content of IgA initially and for the entire monitoring period was within physiological values. The authors found that the levels of immunoglobulins G and M in

elevated and decreased to the initial value by 3 months (**Figure 6a**).

**144**

*(a) The level of immunoglobulin IgA, IgG, and IgM in the blood serum in patients in the dynamics in the postoperative period without splenectomy and (b) the level of immunoglobulin IgA, IgG, and IgM in the blood serum in patients in the dynamics in the postoperative period with a splenectomy.*

patients with gastric cancer who underwent surgical treatment with splenectomy were reduced almost twofold from the baseline, from the 14th day to the 3rd month of **Figure 6b**.

This fact agrees with the data obtained by our study. Change in the immunological repertoire of B2 cell antigens, weak expression of the CD21 membrane antigen, and a significant amount of CD23+ cells in the case of realization of the main pathway of development of antibody producers in response to thymus-dependent antigens may lead to decrease in antibody production.

Among peripheral blood lymphocytes, the presence of CD19+CD5+ B cells (B1a cells), some of which express the activation antigens CD38 and CD23, is found; a small part of CD5+ B cells is CD25+CD38−. Given the membrane immunophenotype circulating in the peripheral blood of B cells, patients with gastric cancer probably have an alternative TH2 response to pathogens.

In the group of patients after surgical intervention in the volume of gastrectomy with standard D2 lymphodissection and splenectomy, the relative total number of CD19+ B lymphocytes and the number of CD19+CD21+ B cells decreased (the differences are close to reliable) compared to preoperative values. In the group of patients with standard D2 lymphodissection and splenectomy, the percentage of CD5+ B lymphocytes significantly increased from 12.9 to 21.8%, after the operation. Given data on B1 and BMZ populations, this can lead to a weakening of both general and antitumor immunity. Since maintaining the population B1 population is very slow, and the renewal of the BMZ pool is possible only in the spleen.

#### **5. Conclusion**

Immunosuppression in patients who underwent surgery (including splenectomy) develops as a result of a disruption in the composition of B cell link. Disorders of the immune response primarily affect the population of B1a lymphocytes, which provides a response to thymus-independent antigens of the second type. Patients in the experimental group may experience decreased production of antibodies, including IgM, which plays an important role in inducing apoptosis of tumor cells.

#### **Conflict of interest**

We hereby inform you that there is no conflict of interest**.**

*Normal and Malignant B-Cell*
