**1. Introduction**

The spleen is one of the most important peripheral organs of the immune system. The content of lymphocytes in the white pulp of the spleen reaches 85% of the total number of cells. This amount is almost 25% of all body's lymphocytes, almost half of them being B cells. Thus, it is the spleen, along with the lymph nodes, which is the organ providing humoral immunity. In the spleen, a red pulp of 70–80% of the body weight is distinguished and white pulp, which accounts for 6–20% of the mass. The red pulp of the spleen is represented by venous sinuses and pulpal strands. In the red pulp, destruction of red blood cells and their absorption by macrophages occur. Lymphocytes predominate in the white pulp of the spleen. They accumulate around the arterioles in the form of so-called periarteriolar clutches. B cell follicles are located closer to the edge of the clutch [1–3].

Complex processes of activation of B cells occur in the spleen. Immature B cells come from the bone marrow to the spleen and lymph nodes, where their further maturation, antigen presentation, proliferation, and differentiation occur. Molecules of IgD, CD21, and CD22 appear on their surface**.**

The process of activation of B cells can be carried out in response to thymus-dependent antigens or without the involvement of a T lymphocyte [4]. T-independent antigens are generally polyvalent lipopolysaccharides, polysaccharides, or proteins. T-independent antigens are divided into type I and type II antigens, which differently ensure the full development of B cells in cells that synthesize antibodies [5–8].

Immature B cells react to T cell-independent antigens of type 1, which elicit a rapid antibody response. Most of mature B cells are within the lymphoid follicles of the spleen and lymph nodes, where they collide and react to T-dependent antigens associated with follicular dendritic cells and proliferate and either differentiate into plasma cells [1].

B cells, specific for autologous antigens, do not enter the follicles; they linger in the outer zone of the periarteriolar lymphoid clutches and die [9]. During the immune response to various antigens, the B lymphocyte-specific immunoglobulin receptor is bound after which the movement of all B cells in the outer zone of the periarteriolar lymphoid clutches has significantly slowed down. Activated B lymphocytes die in the event that there is no interaction with the T cells necessary for the realization of an immune response to thymus-dependent antigens. In the presence of cooperation with T cells, naive B cells enter mainly into follicles, where they undergo differentiation in the germinal centers during primary immune responses.

In secondary immune responses of memory B cells to thymus-dependent antigens, pronounced B cell proliferation and differentiation into plasma cells within the outer zone of periarteriolar lymphoid clutches are observed; follicular B cell proliferation is somewhat weaker than with primary responses [10, 11].

Also in the spleen, there is a special population of cells that delimits white pulp from the red pulp. This area is called the marginal or marginal zone, where both T and B cells are located with a relative predominance of the latter [12]. The population of the B cells of the marginal zone is not homogeneous: it includes naive B cells, as well as B cells of immunological memory, generated both during T-dependent and T-independent antibody responses of the first type [13].

The spleen is the main place for the synthesis of IgM [14–16]. IgM is a polymer in which multiple immunoglobulins are linked together by covalent bonds known as disulfide bonds. IgM-class antibodies are the earliest in immunogenesis and constitute about 6% of all immunoglobulins. The time of their half-life is 5–6.5 days. They are produced by activated B cells at a primary immune response in peripheral lymphoid organs, which also includes lymph nodes and lymphoid formations of mucous membranes [17].

At the same time, the spleen cells are capable of producing various cytokines. In the experiment, it was shown that splenocytes produce interleukin-2, interferongamma, and interleukin-7 during antigen stimulation, which in turn stimulate the proliferation of B cells and the production of immunoglobulins [18].

Surgical treatment of patients with gastric cancer involves the implementation of lymphodissection. The standard volume of lymphodissection for stomach cancer

**135**

*Splenectomy in Gastric Cancer: Influence of B Lymphocytes*

during gastrectomy or proximal resection is D2, which implies a splenectomy that is performed to completely remove the lymph nodes of the spleen gates. However, the splenectomy leads to an increase in the frequency of postoperative complications

The spleen is the largest peripheral organ of the immune system. Immunity disorders can be more pronounced and prolonged after splenectomy. Clinical observations indicate that the improvement of health and clinical and laboratory parameters after splenectomy is in some cases replaced by the development state of immunodeficiency. Currently, this is confirmed experimentally and is referred to in the foreign literature as overwhelming postsplenectomy infections (OPSI) [24–26]. An analogue of the name "overwhelming postsplenectomy infections" is the term "postsplenectomy hypersplenism"; the signs of which are decrease in general tone and performance and

Splenectomy for the purpose of adequate lymphodissection in stomach cancer causes pronounced and long-term dysfunction of various immunity units: the presentation of macrophages by foreign antigens to T and B lymphocytes is disrupted, the subpopulation of B lymphocytes changes, and the levels of all classes of immunoglobulins (IgG, IgA, IgM) decrease [28–30]. However, immunity disorders in patients after splenectomy primarily affect the B cell immune response, including thymus-independent type 2 antigens, which is provided by the population of B1

B1 lymphocytes are relatively small group of B cells, found in humans and mice,

Herzenberg (Hayakawa et al.) as a CD5+ population that differs from normal B (B2) cells by phenotype, anatomical localization, self-healing ability, and the production of natural antibodies. It includes two subpopulations: B1a and B1b [32, 33]. B1

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

Thus, during life, the B1 lymphocyte pool is maintained by the activity of progenitor cells through their very slow proliferation. B1 cells are localized mainly in serous cavities—the abdominal and pleural. Some B1 cells migrate (through the omentum) to the intestinal mucosa and mesenteric lymph nodes (up to 50% of IgA producers in the lymphoid tissue of the intestinal B1cells). In the lymph nodes of the

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

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

and are considered to be the most phylogenetically oldest branch of antibodyproducing cells. The population of B1 cells was first described in 1983 by Lee

lymphocytes develop in the fetal liver from progenitor cells.

characterized by the absence of CD5 expression [36].

and mortality, as confirmed by European randomized trials [19–23].

susceptibility to viral, bacterial, parasitic, and fungal infections [26, 27].

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

lymphocytes [31, 32].

organism [34, 35].

mouse, they are absent.

up to 5% of the number of B cells.

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

*Normal and Malignant B-Cell*

synthesize antibodies [5–8].

the clutch [1–3].

plasma cells [1].

responses.

and their absorption by macrophages occur. Lymphocytes predominate in the white pulp of the spleen. They accumulate around the arterioles in the form of so-called periarteriolar clutches. B cell follicles are located closer to the edge of

Complex processes of activation of B cells occur in the spleen. Immature B cells come from the bone marrow to the spleen and lymph nodes, where their further maturation, antigen presentation, proliferation, and differentiation occur.

Immature B cells react to T cell-independent antigens of type 1, which elicit a rapid antibody response. Most of mature B cells are within the lymphoid follicles of the spleen and lymph nodes, where they collide and react to T-dependent antigens associated with follicular dendritic cells and proliferate and either differentiate into

B cells, specific for autologous antigens, do not enter the follicles; they linger in the outer zone of the periarteriolar lymphoid clutches and die [9]. During the immune response to various antigens, the B lymphocyte-specific immunoglobulin receptor is bound after which the movement of all B cells in the outer zone of the periarteriolar lymphoid clutches has significantly slowed down. Activated B lymphocytes die in the event that there is no interaction with the T cells necessary for the realization of an immune response to thymus-dependent antigens. In the presence of cooperation with T cells, naive B cells enter mainly into follicles, where they undergo differentiation in the germinal centers during primary immune

In secondary immune responses of memory B cells to thymus-dependent antigens, pronounced B cell proliferation and differentiation into plasma cells within the outer zone of periarteriolar lymphoid clutches are observed; follicular B cell

Also in the spleen, there is a special population of cells that delimits white pulp from the red pulp. This area is called the marginal or marginal zone, where both T and B cells are located with a relative predominance of the latter [12]. The population of the B cells of the marginal zone is not homogeneous: it includes naive B cells, as well as B cells of immunological memory, generated both during T-dependent

The spleen is the main place for the synthesis of IgM [14–16]. IgM is a polymer in which multiple immunoglobulins are linked together by covalent bonds known as disulfide bonds. IgM-class antibodies are the earliest in immunogenesis and constitute about 6% of all immunoglobulins. The time of their half-life is 5–6.5 days. They are produced by activated B cells at a primary immune response in peripheral lymphoid organs, which also includes lymph nodes and lymphoid formations of

At the same time, the spleen cells are capable of producing various cytokines. In the experiment, it was shown that splenocytes produce interleukin-2, interferongamma, and interleukin-7 during antigen stimulation, which in turn stimulate the

Surgical treatment of patients with gastric cancer involves the implementation of lymphodissection. The standard volume of lymphodissection for stomach cancer

proliferation is somewhat weaker than with primary responses [10, 11].

and T-independent antibody responses of the first type [13].

proliferation of B cells and the production of immunoglobulins [18].

The process of activation of B cells can be carried out in response to thymus-dependent antigens or without the involvement of a T lymphocyte [4]. T-independent antigens are generally polyvalent lipopolysaccharides, polysaccharides, or proteins. T-independent antigens are divided into type I and type II antigens, which differently ensure the full development of B cells in cells that

Molecules of IgD, CD21, and CD22 appear on their surface**.**

**134**

mucous membranes [17].

during gastrectomy or proximal resection is D2, which implies a splenectomy that is performed to completely remove the lymph nodes of the spleen gates. However, the splenectomy leads to an increase in the frequency of postoperative complications and mortality, as confirmed by European randomized trials [19–23].

The spleen is the largest peripheral organ of the immune system. Immunity disorders can be more pronounced and prolonged after splenectomy. Clinical observations indicate that the improvement of health and clinical and laboratory parameters after splenectomy is in some cases replaced by the development state of immunodeficiency. Currently, this is confirmed experimentally and is referred to in the foreign literature as overwhelming postsplenectomy infections (OPSI) [24–26]. An analogue of the name "overwhelming postsplenectomy infections" is the term "postsplenectomy hypersplenism"; the signs of which are decrease in general tone and performance and susceptibility to viral, bacterial, parasitic, and fungal infections [26, 27].

Splenectomy for the purpose of adequate lymphodissection in stomach cancer causes pronounced and long-term dysfunction of various immunity units: the presentation of macrophages by foreign antigens to T and B lymphocytes is disrupted, the subpopulation of B lymphocytes changes, and the levels of all classes of immunoglobulins (IgG, IgA, IgM) decrease [28–30]. However, immunity disorders in patients after splenectomy primarily affect the B cell immune response, including thymus-independent type 2 antigens, which is provided by the population of B1 lymphocytes [31, 32].

B1 lymphocytes are relatively small group of B cells, found in humans and mice, and are considered to be the most phylogenetically oldest branch of antibodyproducing cells. The population of B1 cells was first described in 1983 by Lee Herzenberg (Hayakawa et al.) as a CD5+ population that differs from normal B (B2) cells by phenotype, anatomical localization, self-healing ability, and the production of natural antibodies. It 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 localized mainly in serous cavities—the abdominal and pleural. Some B1 cells migrate (through the omentum) to the intestinal mucosa and mesenteric lymph nodes (up to 50% of IgA producers in the lymphoid tissue of the intestinal B1cells). In the lymph nodes of the mouse, they are absent.

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 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.

To study the peculiarities of the B cell link in patients with gastric cancer after splenectomy, the subpopulation composition of B lymphocytes was analyzed. The study included two groups of patients who underwent surgery. The first group of patients received treatment in the volume of gastrectomy with spleen-protective D2 lymphodissection. In the second group, patients underwent gastrectomy with D2 lymphodissection and splenectomy. The study of subpopulations of B lymphocytes was carried out at the preoperative stage and 3 months after the surgical treatment.
