Development of B-cell memory in early childhood and the impact on antigen-specific tolerance after heart transplantation

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• 作者：Simon Urschel ; MD^a ; ^b ; ^c ; ¹ ; ^{urschel@ualberta.ca" class="auth_mail" title="E-mail the corresponding author} ; Lauren A. Ryan ; MD^a ; ^b ; Ingrid M. Larsen ; RN^a ; ^b ; Kimberley Biffis ; MSc^a ; ^b ; I. Esme Dijke ; PhD^a ; ^b ; ¹ ; Lori J. West ; MD ; DPhil^a ; ^b ; ^c ; ^d ; ¹
• 关键词：ABO incompatible transplantation ; tolerance ; immature immune system ; memory B-cells ; polysaccharide response ; T-independent B-cell activation ; pediatric heart transplantation
• 刊名：Journal of Heart and Lung Transplantation
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：35
• 期：4
• 页码：491-499
• 全文大小：1771 K

文摘

Young children show better survival after heart transplant compared with older individuals and can receive heart transplants safely from ABO-incompatible donors. Children develop immunologic tolerance to donor ABH antigens reflected in persistent absence of specific antibodies. We hypothesized that immature T-independent B-cell response and lack of B-cell memory play a crucial role in tolerance of ABH antigens after ABOi transplants.

Methods

We determined phenotypes of splenic lymphocytes from adults and children and peripheral blood from ABO-incompatible or ABO-compatible heart transplant recipients and control subjects by flow cytometry. In vitro immune response to T-independent stimulation, erythrocytes, and ABH antigens was assessed using proliferation assays.

Results

A predominant role for CD27⁺ B cells in T-independent activation was demonstrated; these cells were significantly less frequent in infants than older subjects. Only IgM⁺CD27⁺ B cells proliferated in response to non-self erythrocytes. In blood, IgM⁺ and switched IgM⁻ memory B cells were rare in infants, increasing to near-adult levels in children 5 years old. IgM⁺CD27⁺ B cells were significantly fewer in ABO-incompatible transplant recipients than in ABO-compatible recipients.

Conclusions

CD27⁺ cells play a key role in T-independent B-cell activation. Response to ABH antigens is mediated by IgM⁺CD27⁺ B cells, and donor ABO-specific tolerance after ABO-incompatible transplantation in children is facilitated by low prevalence of these cells. The pattern of B-cell memory development is altered after ABO-incompatible transplant. Memory B cells may be quantified to assess eligibility for ABO-incompatible transplant and represent a potential therapeutic target to extend the benefits of the immature immune system to older age groups.